Browse Articles

Prevalence and impact of thyroid dysfunction in patients with rheumatoid arthritis

Abstract Thyroid disorders are common in patients with autoimmune diseases such as rheumatoid arthritis (RA). Both conditions present significant public health concerns due to their impact on quality of life and increased mortality. The aim of this study was to assess the prevalence of thyroid abnormalities in and investigate their influence on rheumatoid arthritis characteristics. This was a case–control study involving adult female patients with RA and age-matched healthy controls. RA disease activity was evaluated using the Disease Activity Score (DAS28), and functional impact was assessed using the Health Assessment Questionnaire (HAQ). Serum thyroid function tests were performed, including thyroid-stimulating hormone (TSH), free thyroxine (FT4), and antithyroid antibodies (TAAs), including anti-thyroglobulin antibodies (TgAb), anti-thyroperoxidase antibodies (TPOAb), and TSH receptor antibodies (TRAb). The study included 58 female RA patients, with a mean age of 52 ± 14.2 years. The median disease duration was 10.41 years. The median DAS28-CRP was 4.03, and the median HAQ was 1.34. The median FT4 and TSH levels were 15.01 [13.48;16.71] and 1.42 [0.91;2.26], respectively. Thyroid dysfunction was identified in 19% of the participants, with hypothyroidism being the most common disorder (17%). Hyperthyroidism was observed in 2% of patients. Antithyroid antibodies were positive in 15.5% (n = 9) of participants, with TPOAb present in 6 patients (10.3%), TgAb in 3 patients (5.2%), and TRAb in 2 patients (3.4%). No statistically significant association was found between thyroid status and RA disease activity, functional impact, or serological status. Despite the lack of correlation, the high prevalence of thyroid dysfunction underscores the importance of regular thyroid screening to optimize management and prognosis in RA patients.

Plant derived extract loaded nanostructured lipid carriers with enhanced oral delivery for the treatment of acute inflammation

Abstract Xanthorrhizol and curcumin are bioactive compounds derived from plants, including Curcuma xanthorrhiza , a member of the ginger family. However, their limited solubility leads to low oral bioavailability and poses significant constraints for industrial applications. Therefore, we developed nanostructured lipid carriers (NLCs) loaded with standardized ethanolic Curcuma xanthorrhiza extract (CXE). The CXE-NLCs were optimized by varying the initial concentration of CXE, resulting in homogeneous particles with a size of 130.0 ± 1.0 nm and a high encapsulation efficiency of approximately 83%. CXE-NLCs exhibited enhanced biostability under simulated gastrointestinal conditions, and in vitro release studies demonstrated the sustained release of CXE. Additionally, CXE-NLCs demonstrated significantly improved permeability across the Caco-2/HT-29 cell monolayer (P app = 4.2 × 10 − 5 cm/s), which is favorable for the oral delivery of bioactive compounds. In vivo studies confirmed that CXE-NLCs inhibited carrageenan-induced inflammation in the paw, prostaglandins E 1 and E 2 , as well as the eicosanoid and MAPK pathways in a dose-dependent manner. This study highlights the enhanced oral delivery and bioactivity of synthesized CXE-NLCs containing both xanthorrhizol and curcumin in the treatment of acute inflammation. This indicates a useful application and suggests their potential as a nano delivery system for nutraceuticals and pharmaceuticals.

Mapping postpartum physical activity, sedentary time, and sleep: assessing the impact of prenatal physical activity interventions in the FitMum randomized controlled trial

Comprehensive bioinformatics analysis reveals prognostic significance and immunological roles of WNT gene family in breast cancer

Abstract Breast cancer (BRCA) is one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths among women worldwide. Previous studies have shown that the WNT (wingless type) gene family plays a role in the development of various cancers. However, comprehensive analysis of WNTs in BRCA remains largely unexplored. In this study, we examined the expression patterns, clinical relevance, and survival outcomes associated with the WNT family and identified key prognostic WNTs. We further investigated genetic alterations, DNA methylation, and drug sensitivity using cBioPortal, SMART, and GSCA databases. Data from GEO and DepMap were used for validation. Our findings revealed that while WNT2 and WNT7B were significantly upregulated and WNT11 was downregulated, WNT2 paradoxically correlated with favorable prognosis despite its oncogenic overexpression. Amplification was the most common type of alteration among the key WNTs selected for analysis and was correlated with immune infiltration and immunotherapy-related biomarkers. Functional enrichment analysis uncovered a novel connection between WNT signaling and neurodegenerative pathways. Furthermore, co-expression and drug sensitivity analyses revealed that WNTs influence the efficacy of multiple anti-cancer agents, offering potential targets for precision oncology. This study provides novel insights into the multifaceted role of WNT genes in BRCA, identifying them as promising prognostic indicators and immunotherapeutic targets that warrant further clinical exploration.

Kinetic-roughening diagrams between Kardar–Parisi–Zhang–like and Berezinskii–Kosterlitz–Thouless rough surfaces for steady crystal growth

Abstract Surface roughness at the nanometer scale influences various phenomena such as the morphology of crystallites at the micrometer scale, the structure factor in X-ray scattering, and backscattering in lidar used for passive remote sensing of ice clouds. In this study, the surface roughness and its roughness exponent are calculated for nano-scale two-dimensional surfaces in three dimensions during the steady growth of crystals using the Monte Carlo method on a lattice model. By monitoring the roughness exponent, slope-dependent kinetic roughening diagrams are constructed for universality classes. The diagrams provide insight into the intricate relationship between the roughness exponent and surface slope, as well as the driving force for crystal growth. The resulting diagrams reveal that at low temperatures, two Kardar–Parisi–Zhang (KPZ)-like kinetic roughening regions, KPZ-like1 and KPZ-like2, are separated by a region of Berezinskii–Kosterlitz–Thouless (BKT) roughening. At high temperatures close to but below the thermal roughening transition temperature of the (001) surface, another KPZ-like region, KPZ-like3, emerges for large driving forces for crystal growth. The terrace width histogram and surface height difference distribution function were also calculated using the Monte Carlo method and provide insight into how the surface crosses over to other classes or subclasses.

Salt rock creep deformation forecasting using deep neural networks and analytical models for subsurface energy storage applications

Hydrogel dressing containing natural extracts inhibits dual-species biofilms of Staphylococcus aureus and Acinetobacter baumannii in ex vivo wound infection models

ID8 cells manifest phenotypic plasticity and molecular heterogeneity of high-grade serous ovarian cancer in response to the local tissue niche

Finite-discrete element numerical modeling on shield tunnel face stability undercrossing existing pipeline considering discontinuous contact

Abstract Tunnel face stability is critical for excavation safety when undercrossing a pipeline. Previous studies inadequately address soil-pipeline discontinuous contact effects. This study elucidates instability mechanisms using coupled FDM-DEM simulations calibrated by physical tests. Results reveal pipeline-induced sheltering effects on failure modes, with sheltered zones transitioning from inverted triangular to spindle-shaped as h/D decreases from 0.5 to 0.1. Evolution of contact force chains show reduced forces ahead of tunnel face and beneath the pipeline drive instability. Surface settlement develops dual troughs flanking the pipeline as δ/D increases from 0.86 to 6.52%. Limit support pressure demarcates three stages at 0.9σ T0 and 0.2σ T0. Crucially, discontinuous contact governs deformation: when ground deformation exceeds pipeline displacement, void-induced separation triggers stress loosening. Parametric studies confirm vertical spacing and flexural stiffness influence pipeline settlements. Controlling face support pressure to prevent excessive discontinuous contact is essential for pipeline safety, providing insights for urban tunnelling adjacent to existing structures.

GENEOnet: a breakthrough in protein binding pocket detection using group equivariant non-expansive operators

Abstract Structure-based virtual screening approaches like molecular docking rely on accurately identifying and precisely calculating binding pockets to efficiently search for potential ligands. In this paper, we introduce GENEOnet, a machine learning model designed for volumetric protein pocket detection that employs Group Equivariant Non-Expansive Operators (GENEOs). These operators simplify model complexity and enable more informed domain knowledge integration by selecting specific physical and chemical properties for each operator to focus on, as well as how they should react. Unlike other methods in this field, GENEOnet has fewer model parameters, resulting in reduced training costs, and offers greater explainability, allowing the parameters to be easily interpreted. GENEOnet processes the empty space within a protein by converting it into a 3D grid of uniform blocks, known as ‘voxels’. It then identifies regions of the grid with an output value above a threshold, thus producing a list of predicted pockets, ranked according to the model’s average output value. Our experimental results show that GENEOnet performs robustly even with small training datasets of 200 proteins and surpasses other established state-of-the-art methods in various metrics. Specifically, GENEOnet’s $$H_1$$ score indicating the probability that the top-ranked pocket is the correct one is 0.764, compared to 0.702 for P2Rank, the next best performing algorithm on our PDBbind test set. Moreover, a case study considering various ABL1 kinase conformations demonstrates the excellent agreement between GENEOnet’s predictions and experimental sites. GENEOnet is available as a web service at https://geneonet.exscalate.eu, where users can access the pre-trained model for detecting and ranking protein cavities.

Design and catalytic performance of a novel two-dimensional copper metal-organic framework for green synthesis of tetrahydrobenzo[b]pyrans

Abstract This study explores development and using a novel two-dimensional metal-organic framework (2D MOF) as a heterogeneous catalyst in organic synthesis. The phosphonocarboxylic acid m -PO 3 CH 2 C 6 H 4 CO 2 H (MPB) has been employed in synthesizing a metal carboxyarylphosphonate. The 2D MOF [Cu(H 2 O)( m -PO 3 CH 2 C 6 H 4 CO 2 H)] n was synthesized in both crystal (Cu-MPB) and nanostructure (Cu-MPB′) forms, characterized by X-ray single crystallography, SEM, TGA, FT-IR, PXRD, EDX, Mapping, and nitrogen adsorption-desorption, and employed for the efficient green synthesis of tetrahydrobenzo[b]pyrans. The crystal structure features alternating inorganic and organic layers. The organic layers have supramolecular dimers of carboxylic acid groups, two molecules bonded to two inorganic layers. Tetrahydrobenzo[b]pyran yield optimization conditions were determined with water/ethanol as solvents, using a catalyst loading of 0.06 g for 95% yields. The fabricated catalyst exhibited exceptional catalytic performance, wide applicability to different aldehyde substrates, and remarkable reusability, achieving high yields for as many as seven cycles post-reaction. In comparison to earlier catalytic systems, the compound Cu-MPB′ showed enhanced efficiency and recyclability. These results underscore the promise of this innovative 2D MOF in promoting sustainable and effective organic synthesis.

Strontium and oxygen isotope analysis reveals changing connections to place and group membership in the world’s earliest village societies

Abstract The Neolithic of southwest Asia, 11,600–7500 years ago, charts the earliest establishment of permanent settlements and changes in food procurement and community structure that transformed human lifeways. Our understanding of the social behaviors that impacted these shifting connections to place and group membership can be improved by studying how people moved across landscapes. Parts of southwest Asia have shown contrasting evidence for mobility practices, but little is known from the Northern Levant, a region key to the development and transmission of agriculture and settled life, particularly for the latest Neolithic stages. We measured strontium and oxygen isotope values in 71 human teeth from five archeological sites in Syria, spanning the entire Neolithic period. A shift to broadly local communities following the establishment of village life suggests consolidation of group membership and deep connections to particular locales, perhaps aimed at social cohesion. Mobility then increases in the later Neolithic, explaining the high degree of cross-regional connectivity witnessed archeologically. A sex-bias towards female mobility during this period may point towards the formation of patrilocal traditions. At our sites both non-local and local individuals were afforded similar burial treatment, suggesting inclusivity in group membership and mobile individuals connecting to new places in the landscape.

Effects of temporal, geographical and environmental factors on salmon lice (Lepeophtheirus salmonis) levels of Atlantic salmon (Salmo salar) in Ireland

Morphotype-based risk stratification in patients with patent foramen ovale using computational fluid dynamics

Quantitative spatial analysis of crystallin proteins in human lens epithelial cells

Abstract Resolving spatial protein dynamics in native human epithelial tissues presents a significant technical challenge, particularly in inherently curved or unevenly mounted specimens. Here, we introduce an image processing pipeline for high-resolution, compartment-based analysis of protein localization, using the native three-dimensional architecture of the human anterior lens epithelium and capsule complex as a robust ex vivo proof-of-principle platform for precise cell segmentation and quantitative analysis. This platform integrates whole-mount immunostaining, 3D confocal imaging, computational tissue flattening, digital segmentation, and spatial regression to quantitatively map subcellular protein distributions at the tissue scale. To demonstrate the utility of this approach, we examined the spatial distribution of αB-crystallin (CRYAB), a stress-associated small heat shock protein, and βB2-crystallin (CRYBB2), a predominantly structural lens protein, in specimens obtained during cataract surgery. We observed a marked accumulation of CRYAB in epithelial cells at the capsule edge following both laser and manual capsulorhexis, indicating a localized stress response to surgical intervention. In contrast, CRYBB2 distribution remained unaffected. Furthermore, both proteins exhibited consistent cytoplasmic localization, while only CRYBB2 occasionally showed exclusive nuclear accumulation. This pipeline offers a scalable framework for quantitatively resolving protein localization in native epithelial architectures, using CRYAB and CRYBB2 as examples of how stress-associated changes can be spatially mapped in situ within the human lens.

Bridging training and practice gap: A mixed methods tracer study of bachelor of science in nursing graduates (2016–2020) at Kairuki University, Dar es Salaam, Tanzania

Background Tracer studies evaluate the effectiveness of university training by assessing how graduates perform in the job market. This study focused on Bachelor of Science in Nursing (BScN) graduates, aiming to describe their training experiences, application of acquired competencies, and overall stakeholder perceptions to inform BScN curriculum improvement. Methods A convergent parallel mixed-method design was used to collect quantitative and qualitative data concurrently from 2016–2020 BScN graduates (February-May 2023). Graduates and other stakeholders (including educators, employers, and policymakers) in this study were selected from private, public, and faith-based hospitals and universities, colleges, and the Ministry of Health. Quantitative data were gathered via online structured questionnaires adapted and modified from the American International Health Alliance and the Technical Vocational Education and Training tools. Qualitative data were collected through interviews and focus groups with graduates, employers, educators, and policymakers. Quantitative data were analyzed using descriptive statistics, while qualitative data underwent thematic analysis. Integration occurred during interpretation to provide a comprehensive understanding of graduates’ experiences, competency application, and stakeholder perceptions of the BScN program. Results Among the 61 graduates who completed the online survey, 37 (60.7%) were female. Most (48; 78.7%) worked as nurses, while 6 (9.8%) were tutors and 3 (4.9%) worked as tutorial assistants. Demonstration was rated the most useful teaching and learning method by 52 (85.2%) respondents, and 47 (81%) rated practical exams as a useful assessment method. These were also supported by graduates and stakeholders who shared their perspectives with regard to the benefits and impact of the BScN program and training quality. Additionally, 54 graduates (94.7%) found the program very useful in preparing them for their professional roles, which aligned with their views on the connection between acquired competencies and job performance. Both graduates and educators highlighted challenges encountered during training and in professional practice. Policymakers and graduates also offered recommendations for improving the program. Additionally, 54 graduates (94.7%) found the program very useful in preparing them for their professional roles, which aligned with their views on the connection between acquired competencies and job performance. Both graduates and educators highlighted challenges encountered during training and in professional practice. Policymakers and graduates also offered recommendations for improving the program. Conclusion The findings demonstrate that the BScN program is widely regarded by graduates and stakeholders as effective in preparing students for professional practice, particularly through practical teaching methods such as demonstrations and practical exams. While the program’s impact on competency development and job performance was strongly affirmed, the study also revealed notable challenges during training and practice. These insights support the ongoing review and enhancement of the BScN curriculum.

Supercooled storage of red blood cells slows down the metabolic storage lesion

Gardenia jasminoides fruit extract ameliorates non-alcoholic steatohepatitis with fibrosis by modulating inflammatory and fibrogenic pathways

Despite advances in drug development, treatment for non-alcoholic steatohepatitis (NASH)-related liver fibrosis remains limited, underscoring the need for more effective therapeutic strategies. Gardenia jasminoides exhibits promising anti-inflammatory and anti-fibrotic properties, suggesting its potential as a therapeutic candidate for NASH-related liver fibrosis. Accordingly, this study aimed to investigate the therapeutic potential of Gardenia jasminoides fruit extract (GJE) in a rat model of NASH with fibrosis induced by a high-fat, high-fructose (HFHF) diet, and to elucidate the underlying molecular mechanisms. Male Sprague-Dawley rats were randomly assigned to four groups (n = 6/group): 1) Control group, fed a standard diet; 2) NASH with fibrosis group (NF), fed a HFHF diet for 20 weeks; 3) Low-dose GJE group (NF + Low dose GJE), treated with 0.119 g/kg BW of GJE; and 4) High-dose GJE group (NF+High dose GJE), treated with 0.239 g/kg BW of GJE. GJE was administered via intragastric gavage once daily from weeks 13–20. Serum markers of liver injury (ALT and AST) were assessed. Liver histology was examined to evaluate NASH and fibrosis severity. Immunohistochemistry was performed to detect NF-kB p65 and Col1a1 expression and protein levels of MMP-12, α-SMA, IL-13 and TGF-β1 were quantified. Serum ALT and AST levels were significantly increased in the NF group, which also showed the highest NASH histopathology scores and collagen deposition. GJE treatment significantly reduced ALT and AST levels in both low- and high- dose groups. The low-dose GJE group showed marked improvement in NASH histopathology, while both treatment groups exhibited reduced hepatic collagen deposition. GJE treatment significantly suppressed NF-kB p65 and Col1a1 expression, along with downregulation of MMP-12, α-SMA, IL-13 and TGF-β1 protein levels. In conclusion, GJE effectively ameliorated HFHF diet-induced NASH with fibrosis by modulating inflammatory and fibrogenic pathways.

Parasitic Pachypygus gibber poses a silent threat to reproduction and development in Ciona robusta

Revealing the molecular mechanisms underlying Xuebijing against sepsis and septic acute kidney injury via bioinformatics and experimental approaches

Background Sepsis and its related complication acute kidney injury (septic-AKI) are associated with high mortality and morbidity, and have become a global health challenge. Xuebijing (XBJ) injection prepared from five traditional Chinese medicines (TCM) is commonly used for clinical treatment of sepsis and septic-AKI. Yet, the underlying therapeutic mechanism of XBJ is remain elusive. This study aims to unveil the underlying mechanisms of XBJ in treating sepsis and septic-AKI. Methods In this study, we used network pharmacology and molecular docking to screen the core drug-disease targets and predict the potential mechanism involving in XBJ against sepsis and septic AKI. Furthermore, in vitro experiments were performed to verify the predicted results and clarify the underlying mechanism. Results Five hub targets including MMP9, TNF, IL-6, STAT3 and TP53 were identified by constructing and analyzing protein-protein interaction network. Eight key active components linking to five hub targets were also reversely screened. The results of gene ontology (GO) and pathway enrichment analysis showed that on the list of top 10 significant GO terms and pathways, most were inflammatory signaling pathways. The molecular docking results suggested that eight active components more preferentially bound to MMP9 and TNFα with the highest affinity. In vitro, XBJ significantly decreased the mRNA and protein levels of IL-1β, IL-6, TNFα and MMP9 in HEK-293 cells exposed to lipopolysaccharides (LPS). Conclusions XBJ exerted therapeutic effects on sepsis and septic-AKI through suppression IL-1β/MMP9, IL-6/MMP9 and TNFα/MMP9 at both mRNA and protein level. This study provides a pharmacological basis for further validating the therapeutic mechanism of XBJ in treating sepsis and septic-AKI by in vitro and in vivo experiments.