Search Results (630)

The associations between sialylated anti-cyclic citrullinated peptide (anti-CCP) antibodies bearing α-2,6-sialic acid (SIA), ST6Gal1 and Neu1 enzymes, and clinical disease activity measures such as disease activity score 28 (DAS28), the Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) are unknown in rheumatoid arthritis (RA). To address this gap, this study included 97 patients with RA evaluated at baseline (month 0) and at 6 and 12 months. At each visit, blood cells were analyzed for B-cell ST6Gal1 and Neu1 expressions, and plasma samples were assessed for ST6Gal1 and Neu1 levels. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), monocyte chemotactic protein-1 (MCP-1), and IgG anti-CCP with its α-2,6-SIA modification were measured. Disease activity measures, namely DAS28-ESR, DAS28-CRP, DAS28-MCP-1, SDAI, and CDAI, were calculated. Correlations and Receiver Operating Characteristics among ST6Gal, Neu1, SIA/anti-CCP ratios, and disease activity measures were assessed. Multivariate regression analyses were performed to reveal confounding factors in such correlations. The total SIA content of anti-CCP antibodies was inversely correlated with B-cell Neu1 levels (ρ = −0.317 with p = 0.013. Plasma (free-form) Neu1 levels were inversely correlated with SIA/IgG anti-CCP ratios (ρ = −0.361, p = 0.001) in the DAS28-MCP-1 < 2.2 (remission) subgroup. No such correlation was observed for the DAS28-ESR, DAS28-CRP, SDAI, or CDAI subgroups. B-cell ST6Gal1 levels correlated inversely with SDAI ≤ 11 and DAS28-MCP-1 ≤ 3.6 combined remission and low-disease-activity subgroups (ρ = −0.315 with p = 0.001 and ρ = −0.237 with p = 0.008, respectively). The same was observed for B-cell ST6Gal1/Neu1 ratios correlating with the SDAI ≤ 11 subgroup (ρ = −0.261, p = 0.009). Nevertheless, B-cell ST6Gal1/Neu1 ratios against SDAI ≤ 11 and DAS28-MCP-1 ≤ 3.6 subgroups produced significant area-under-curve (AUC) values of 0.616 and 0.600, respectively (asymptotic p-Values 0.004 and 0.018, respectively). Through multivariate regression analyses, we found that biologics (a confounding factor) interfered with p-Values related to the B-cell ST6Gal1 enzyme but did not interfere with p-Values related to the pure B-cell Neu1 enzyme. In addition, disease duration interfered with p-Values related to the pure Neu1 enzyme on B-cells or in plasma. Moreover, plasma ST6Gal1/Neu1 ratios against the DAS28-MCP-1 < 2.2 remission subgroup produced an AUC of 0.628 and asymptotic p = 0.003. Therefore, it is suggested that B-cell ST6Gal1/Neu1 ratios can be used as clinical indicators for the combined remission and low-disease-activity subgroup of SDAI and DAS28-MCP-1 formulae. Plasma ST6Gal1/Neu1 ratios are also good indicators of DAS28-MCP-1 remission. Full article

The renin-angiotensin system (RAS) has evolved from being considered solely a peripheral endocrine system for cardiovascular control to being recognized as a complex molecular network with important functions in the central nervous system (CNS) and peripheral nervous system (PNS). Here we examine the organization, mechanisms of action, and clinical implications of cerebral RAS in physiological conditions and in various neurological pathologies. The cerebral RAS operates autonomously, synthesizing its main components locally due to restrictions imposed by the blood–brain barrier. The key elements of the system are (pro)renin; (pro)renin receptor (PRR); angiotensinogen; angiotensin-converting enzyme types 1 and 2 (ACE1 and ACE2); angiotensin I (AngI), angiotensin II (AngII), angiotensin III (AngIII), angiotensin IV (AngIV), angiotensin A (AngA), and angiotensin 1-7 (Ang(1-7)) peptides; RAS-regulating aminopeptidases; and AT1 (AT1R), AT2 (AT2R), AT4 (AT4R/IRAP), and Mas (MasR) receptors. More recently, alamandine and its MrgD receptor have been included. They are distributed in specific brain regions such as the hypothalamus, hippocampus, cerebral cortex, and brainstem. The system is organized into two opposing axes: the classical axis (renin/ACE1/AngII/AT1R) with vasoconstrictive, proinflammatory, and prooxidative effects, and the alternative axes AngII/AT2R, AngIV/AT4R/IRAP, ACE2/Ang(1-7)/MasR and alamandine/MrgD receptor, with vasodilatory, anti-inflammatory, and neuroprotective properties. This functional duality allows us to understand its role in neurological physiopathology. RAS dysregulation is implicated in multiple neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and neuropsychiatric disorders such as depression and anxiety. In brain aging, an imbalance toward hyperactivation of the renin/ACE1/AngII/AT1R axis is observed, contributing to cognitive impairment and neuroinflammation. Epidemiological studies and clinical trials have shown that pharmacological modulation of the RAS using ACE inhibitors (ACEIs) and AT1R antagonists (ARA-II) not only controls blood pressure but also offers neuroprotective benefits, reducing the incidence of cognitive decline and dementia. These effects are attributed to direct mechanisms on the CNS, including reduction of oxidative stress, decreased neuroinflammation, and improved cerebral blood flow. Full article

Nowadays, with the accumulation of large amounts of stress-response transcriptomic data in plants, it is possible to clarify the key genes and transcription factors (TFs) involved in these processes. Here, we present the comprehensive transcriptomic meta-analysis of the high light (HL) response in photosynthetic tissues of Arabidopsis thaliana (L.) Heynh., offering new insights into adaptation mechanisms of plants to excessive light and involved gene regulatory networks. We analyzed 21 experiments covering 58 HL conditions in total, yielding 218,000 instances of differentially expressed genes (DEGs) corresponding to 19,000 unique genes. Based on these data, we developed the publicly accessible AraLightDEGs resource, which offers multiple search filters for experimental conditions and gene characteristics, and we conducted a detailed meta-analysis using our R pipeline, AraLightMeta. Our meta-analysis highlighted distinct transcriptional programs between short- and long-term HL responses in leaves, revealing novel regulatory interactions and refining the understanding of key DEGs. In particular, long-term HL adaptation involves key TFs such as CRF3 and PTF1 regulating antioxidant and jasmonate signaling; ATWHY2, WHY3, and emb2746 coordinating chloroplast and mitochondrial gene expression; AT2G28450 governing ribosome biogenesis; and AT4G12750 controlling methyltransferase activity. We integrated these findings into a conceptual scheme illustrating transcriptional regulation and signaling processes in leaf cells responding to long-term HL stress. Full article

Background/Objectives: Alport syndrome (AS) predominantly presents with X-linked inheritance worldwide. However, the epidemiological landscape remains poorly characterized, particularly among ethnic minority groups like the Roma minority in Slovakia. Our study aimed to investigate the inheritance patterns of AS in this region and determine whether a distinct pattern predominates. Methods: Selective genetic screening for pathogenic variants previously occurring in Slovakia was performed. Samples from patients with persistent (familial) hematuria ± hearing loss who had not yet undergone biopsy or genetic testing were analyzed by high-resolution melting analysis. The prevalence of AS per million (pm) population was calculated by adding information on patients with previously confirmed AS. Results: Twenty-five new cases of ARAS, one digenic form, and two cases of XLAS were identified by screening. In total, we collected information on 46 patients with genetically or bioptically confirmed AS in the region of eastern Slovakia, corresponding to a prevalence of 29 pm population. The c.1598G>A (p.Gly533Asp) pathogenic variant of the collagen type IV alpha 4 chain, which follows an autosomal recessive inheritance pattern, was the most prevalent variant that was exclusively confirmed in Roma patients (n = 35), suggesting a founder effect. Within the Roma community, the prevalence of ARAS (the most prevalent inheritance pattern) corresponds to 133 pm of the Roma population, based on midpoint population estimates. Conclusions: Our findings demonstrate a unique genetic profile of AS in the Roma population, characterized by a high prevalence of ARAS, with implications for genetic counseling and screening strategies. Full article

A rational synthesis of the branched decaarabinofuranoside with 4-(2-azidoethoxy)phenyl aglycone (a Janus aglycone) related to the non-reducing terminal fragments of the arabinogalactan and lipoarabinomannan from Mycobacterium tuberculosis was proposed. Since the most challenging step is the formation of a 1,2-cis glycosidic linkage, we have significantly simplified access to a library of oligoarabinofuranosides derived from Mycobacterium tuberculosis polysaccharides using a silylated Ara-β-(1→2)-Ara disaccharide as the glycosyl donor. The application of a Janus aglycone also allowed us to reduce the number of reaction steps in glycoside synthesis. The obtained arabinans can be useful to further prepare conjugates as antigens for creating tuberculosis screening assays. Full article

Resistance to cytarabine (Ara-C) remains a major obstacle to the successful treatment of acute myeloid leukemia (AML). Therefore, modulating Ara-C resistance is indispensable for improving clinical outcomes. We previously demonstrated that sodium caseinate (SC), a salt derived from casein, the principal milk protein, inhibits proliferation and modulates the expression of Ara-C resistance-related genes in chemoresistant cells. However, it remains unclear whether the combination of SC with antineoplastic agents enhances apoptosis, modulates chemoresistance-related genes, and prolongs the survival of tumor-bearing mice implanted with chemoresistant cells. Here, we investigated the effects of SC in combination with Ara-C or daunorubicin (DNR) on cell proliferation, apoptosis, the expression of chemoresistance-associated genes, and the survival of tumor-bearing mice. Crystal violet assays, quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunofluorescence, flow cytometry, and Kaplan–Meier survival curves were used to evaluate the effects of combinations in chemoresistant cells. We demonstrate that the IC₂₅ concentration of SC, when combined with antileukemic agents, increases the sensitivity of chemoresistant WEHI-CR50 cells to Ara-C by downregulating SIRT1 and MDR1, upregulating the expression of ENT1 and dCK, enhancing apoptosis, and prolonging the survival of WEHI-CR50 tumor-bearing mice. Our data suggest that SC in combination with antileukemic agents could be an effective adjuvant for Ara-C-resistant AML. Full article

Background and Objectives: The causes and clinical outcomes of renal perfusion abnormalities occurring after para-aortic lymphadenectomy (PANDx) for gynecologic malignancies are unknown. We investigated the potential involvement of accessory renal artery (ARA) obstruction in their development by reassessing perioperative contrast-enhanced computed tomography (CECT). Materials and Methods: This retrospective study investigated a clinical database to identify urinary contrast defects using CECT in all patients who had undergone PANDx between January 2020 and December 2024. The perfusion defects in the kidney detected by CECT were extracted by a gynecologic oncologist and evaluated by a radiologist and urologist for suspected obstruction of ARAs. Results: Postoperative renal contrast defects were observed in 3.8% (6/157) of patients. Renal parenchymal fibrosis, cortical atrophy, and parenchymal thinning were observed as universal findings in all patients showing renal contrast defects. In five of the six cases, ARAs supplying the infarcted renal segments were identified on preoperative CECT, and arterial obstruction was confirmed on postoperative imaging. The remaining case was considered to be latent pyelonephritis. All five patients underwent laparotomy, and preoperative CECT failed to detect ARAs. The median resected para-aortic lymph node was 23 nodes (range: 15–33) in five patients, showing no statistically significant difference compared to patients without perfusion abnormalities (p = 0.19). Postoperative serum creatinine levels remained stable. Conclusions: ARA obstruction appears to be a risk factor for segmental renal infarction after para-aortic lymphadenectomy in gynecological malignancies; however, the clinical impact on urinary function may be limited. Awareness of this potential complication is essential for gynecologic oncologists performing PANDx. Full article

This paper presents the integrated study of the funerary ara of Ofilius Ianuarius, discovered within the burial complex of Via Appia Antica 39, and explores its digital stratigraphic recontextualisation through two 3D semantic workflows. The research aims to evaluate the potential of stratigraphic 3D modelling as a tool for post-excavation analysis and transparent archaeological interpretation. Starting from a set of georeferenced photogrammetric models acquired between 2023 and 2025, the study tests two workflows: (1) an EMF-based approach using the Extended Matrix, Blender, and EMviq for stratigraphic relationship modelling and online visualisation; (2) a semantic integration method using the .gltf format and the CRMArcheo Annotation Tool developed in Blender, exported to the ATON platform. While both workflows enable accurate 3D documentation, they differ in their capacity for structured semantic enrichment and interoperability. The results highlight the value of combining reality-based models with semantically linked stratigraphic proxies and suggest future directions for linking archaeological datasets, ontologies, and interactive digital platforms. This work contributes to the ongoing effort to foster transparency, reproducibility, and accessibility in virtual archaeological reconstruction. Full article

Background and Objectives: We wished to evaluate the effect of antiresorptive agents (ARAs) on peri-implant tissues and to examine the risk factors for peri-implant medication-related osteonecrosis of the jaw (MRONJ). Materials and Methods: The study cohort consisted of patients who underwent implant surgery or maintenance treatment between March 2012 and December 2024. The patients were divided into two groups: those in whom bisphosphonates (BPs) or denosumab (Dmab) was used to treat osteoporosis after implant treatment (the ARA group) and a control group. Peri-implant clinical parameters (implant probing depth (iPPD), implant bleeding on probing (iBoP), marginal bone loss (MBL), and mandibular cortical index (MCI)) measured at the baseline and at the final visit were statistically evaluated and compared in both groups. Risk factors were examined using a multivariate analysis of adjusted odds ratios (aORs). Results: A total of 192 implants in 61 patients (52 female, 9 male) were included in this study. The ARA group consisted of 89 implants (22 patients). A comparison of the clinical parameters showed that the ARA group had significantly higher variations in their maximum iPPD and iBoP values over time than those in the control group. Risk factors for peri-implantitis as objective variables were the use of ARAs (aOR: 3.91; 95% confidence interval [CI]: 1.29–11.9) and the change in the maximum iPPD over time (aOR: 1.86; 95% CI: 0.754–4.58). Conclusions: During long-term implant maintenance treatment, patients’ health and medication status change. Monitoring peri-implantitis, the presumed cause of peri-implant MRONJ, is essential, especially in patients who started ARA treatment after implant placement, and special attention should be paid to changes in implant pocket depth. Full article

Ultraviolet B (UVB) irradiation drives skin photodamage, prompting exploration of natural therapeutics. This study investigated the reparative effects and mechanisms of crude Gastrodia elata polysaccharides (GP) on UVB-induced acute skin damage. GP was extracted from fresh G. elata via water extraction and alcohol precipitation. It is a homogeneous polysaccharide with a weight-average molecular weight of 808.863 kDa, comprising Ara, Glc, Fru, and GalA. Histopathological analysis revealed that topical application of GP on the dorsal skin of mice effectively restored normal physiological structure, suppressing epidermal hyperplasia and collagen degradation. Biochemical assays showed that GP significantly reduced the activities of MPO and MDA following UVB exposure while restoring the enzymatic activities of SOD and GSH, thereby mitigating oxidative stress. Moreover, GP treatment markedly upregulated the anti-inflammatory cytokines TGF-β and IL-10 and downregulated the pro-inflammatory mediators IL-6, IL-1β, and TNF-α, suggesting robust anti-inflammatory effects. Transcriptomics revealed dual-phase mechanisms: Early repair (day 5) involved GP-mediated suppression of hyper inflammation and accelerated necrotic tissue clearance via pathway network modulation. Late phase (day 18) featured enhanced anti-inflammatory, antioxidant, and tissue regeneration processes through energy-sufficient, low-inflammatory pathway networks. Through a synergistic response involving antioxidation, anti-inflammation, promotion of collagen synthesis, and acceleration of skin barrier repair, GP achieves comprehensive repair of UVB-induced acute skin damage. Our findings not only establish GP as a potent natural alternative to synthetic photoprotective agents but also reveal novel pathway network interactions governing polysaccharide-mediated skin regeneration. Full article

Background: Fish escape events from aquaculture facilities are increasing and pose significant ecological, economic, and traceability concerns. Accurate methods to differentiate between wild, cultured, and escaped fish are essential for fishery management and seafood authentication. Methods: This study analyzed muscle tissue from Sparus aurata, Dicentrarchus labrax, and Argyrosomus regius using a multiomics approach. Heavy metals were quantified by ICP-MS, fatty acid profiles were assessed via GC-MS, and metabolomic and lipidomic signatures were identified using 1H NMR spectroscopy. Multivariate statistical models (MDS and PLS-LDA) were applied to classify fish origins. Results: Wild seabream showed significantly higher levels of arsenic (9.5-fold), selenium (3.5-fold), and DHA and ARA fatty acids (3.2-fold), while cultured fish exhibited increased linoleic and linolenic acids (6.5-fold). TMAO concentrations were up to 5.3-fold higher in wild fish, serving as a robust metabolic biomarker. Escaped fish displayed intermediate biochemical profiles. Multivariate models achieved a 100% classification accuracy across species and analytical techniques. Conclusions: The integration of heavy metal analysis, fatty acid profiling, and NMR-based metabolomics enables the accurate differentiation of fish origin. While muscle tissue provides reliable biomarkers relevant to human exposure, future studies should explore additional tissues such as liver and gills to improve the resolution of traceability. These methods support seafood authentication, enhance aquaculture traceability, and aid in managing the ecological impacts of escape events. Full article

This study investigates eye movement patterns as indicators of text complexity in Arabic, focusing on the comparative analysis of Classical Arabic (CA) and Modern Standard Arabic (MSA) text. Using the AraEyebility corpus, which contains eye-tracking data from readers of both CA and MSA text, we examined differences in fixation patterns, regression rates, and overall reading behavior between these two forms of Arabic. Our analyses revealed significant differences in eye movement metrics between CA and MSA text, with CA text consistently eliciting more fixations, longer fixation durations, and more frequent revisits. Multivariate analysis confirmed that language type has a significant combined effect on eye movement patterns. Additionally, we identified different relationships between text features and eye movements for CA versus MSA text, with sentence-level features emerging as significant predictors across both language types. Notably, we observed an interaction between language type and readability level, with readers showing less sensitivity to readability variations in CA text compared to MSA text. These findings contribute to our understanding of how historical language evolution affects reading behavior and have practical implications for Arabic language education, publishing, and assessment. The study demonstrates the value of eye movement analysis for understanding text complexity in Arabic and highlights the importance of considering language-specific features when studying reading processes. Full article

The search for alternative sources of biologically active compounds of plant origin, including phenolic compounds (PCs), is of great importance in medicine and pharmacology. Morphophysiological characteristics, photosynthetic pigments, PCs content, phenolic profile, as well as antioxidant (AOA) and antiradical activity (ARA), were studied for in vitro rhododendrons’ microshoots (R. smirnowii, R. PJM Elite, R. japonicum). The microshoots of R. PJM Elite had the highest photosynthetic pigments content (chlorophylls a and b), exceeding that of R. smirnowii and R. japonicum, it was 33% and 42%, respectively. The total phenolic content increased in the row R. PJM Elite < R. smirnowii < R. japonicum. Twelve to twenty phenolic compounds were identified in ethanol extracts of rhododendron microshoots, using high-performance liquid chromatography. Quercetin, kaempferol, and myricetin dominated in the phenolic complex of R. japonicum and R. smirnowii, whereas in R. PJM Elite, they were taxifolin and (−)-epicatechin. The AOA and ARA evaluation in DPPH-radical system and the model of initiated liposomes oxidation allowed to determine the highest activity in both systems for R. japonicum extracts, which was not typical for the other two species extracts. A high correlation was found between AOA extracts and the flavonoid content in them. The results obtained indicate the prospects of using R. japonicum and R. PJM Elite microshoots as an alternative source of flavonols and flavanols, accordingly. Full article

This study reports a successful selective waste collection initiative led by UFSC’s Araranguá campus in a municipality without a recycling system. The initiative, named “Recicla UFSC Ara”, was structured around three main components: (i) the installation of color-coded bins for recyclable waste (including paper, plastic, metals, and polystyrene) and non-recyclable waste in indoor and common areas; (ii) the establishment of a Voluntary Delivery Point (PEV) to gather specific recyclable materials, such as glass, electronics waste, plastic bottles, writing instruments, and bottle caps; and (iii) the execution of periodic educational community-focused campaigns aimed at encouraging participation from both the university and the broader local community. Recyclables were manually sorted and weighed during regular collection rounds, and contamination rates were calculated. Quantitative data collected from 2022 to 2025 were analyzed using descriptive statistics and one-way ANOVA to assess waste generation and contamination trends. Gathered recyclables were directed to appropriate partner institutions, including local “Ecoponto”, non-profit organizations, and corporate recycling programs. The study also conducted a literature review of similar university-led waste management programs to identify standard practices and regional specificities, providing a comparative analysis that highlights both shared elements and distinctive contributions of the UFSC model. Results demonstrate a significant volume of waste diverted from landfills and a gradual improvement in waste disposal practices among the university community. Targeted communication and operational changes mitigated key challenges, improper disposal, and logistical issues. This case underscores the role of universities as agents of environmental education and local sustainable development. Full article

Human–computer interaction (HCI) plays a crucial role across various fields, with eye-tracking technology emerging as a key enabler for intuitive and dynamic control in assistive systems like Assistive Robotic Arms (ARAs). By precisely tracking eye movements, this technology allows for more natural user interaction. However, current systems primarily rely on the single gaze-dependent interaction method, which leads to the “Midas Touch” problem. This highlights the need for real-time eye movement classification in dynamic interactions to ensure accurate and efficient control. This paper proposes a novel Gaussian Mixture Model–Hidden Markov Model (GMM-HMM) classification algorithm aimed at overcoming the limitations of traditional methods in dynamic human–robot interactions. By incorporating sum of squared error (SSE)-based feature extraction and hierarchical training, the proposed algorithm achieves a classification accuracy of 94.39%, significantly outperforming existing approaches. Furthermore, it is integrated with a robotic arm system, enabling gaze trajectory-based dynamic path planning, which reduces the average path planning time to 2.97 milliseconds. The experimental results demonstrate the effectiveness of this approach, offering an efficient and intuitive solution for human–robot interaction in dynamic environments. This work provides a robust framework for future assistive robotic systems, improving interaction intuitiveness and efficiency in complex real-world scenarios. Full article