Search Results (531,836)

Objectives: To assess the incidence rate of anterior acute uveitis (AAU) in patients with longstanding axial spondyloarthritis (axSpA); to evaluate demographic and clinical characteristics associated with AAU development; and to determine the influence of AAU on bDMARD initiation and retention in this population. Methods: This two-timepoint cohort study analysed data from patients enrolled in the Spanish SpA registry REGISPONSER (2004–2007), who were re-evaluated 17 years later in the REGISPON-3 follow-up study (2021–2023). Information on the date of first AAU episode and bDMARD initiation was collected. Kaplan–Meier and Cox proportional hazards models were used to assess AAU incidence, predictors, and its association with time to bDMARD initiation and treatment retention. Results: A total of 299 patients with longstanding axSpA were included, of whom 33.4% experienced at least one episode of AAU, corresponding to an incidence rate of 1.15 per 100 person-years. The cumulative probability of a first episode of AAU increased with disease duration. The relative risk for developing a second episode after the first, compared to the overall risk of any episode in the total population, was 1.85 (95% CI: 1.34–2.57). In multivariable cox analysis, female sex and baseline enthesitis were independently associated with a higher risk of AAU. AAU did not significantly affect the likelihood of subsequent bDMARD initiation, with similar cumulative treatment probabilities in patients with and without AAU. Among treated patients, adalimumab was more frequently prescribed in those with a history of AAU. bDMARD retention rates at two and five years were comparable regardless of AAU status, suggesting that AAU was not associated with long-term treatment persistence. Conclusions: In patients with longstanding axSpA, the incidence of AAU increased steadily over time. However, the presence of AAU did not significantly influence bDMARD initiation or long-term retention in routine clinical practice. Full article

Melanoma is an aggressive malignancy with poor prognosis in advanced stages, and current therapeutic options provide only limited benefits, highlighting the need for novel treatments. Chetomin, a fungal metabolite isolated from Chaetomium cochliodes, has been reported to exhibit diverse biological activities, yet its effects on melanoma cells remain poorly understood. In this study, we evaluated the antitumor potential of chetomin using the human A375 melanoma cell line. Cell viability was assessed with MTT and CellTiter-Glo^® assays, which revealed a significant dose- and time-dependent reduction in proliferation following chetomin exposure. Apoptotic effects were confirmed through Annexin V staining, and immunocytochemical analysis demonstrated a concentration-dependent increase in cleaved PARP1, indicating activation of programmed cell death pathways. Collectively, these findings demonstrate that chetomin effectively inhibits melanoma cell growth and promotes apoptosis. The results suggest that chetomin represents a promising lead compound for melanoma therapy, warranting further investigation into its precise molecular mechanisms. Full article

Ectropis grisescens (Lepidoptera: Geometridae) is a destructive pest in tea plantations, leading to significant economic losses through defoliation. Existing control strategies, including chemical insecticides and biological agents, are often limited by environmental concerns, resistance, and variable efficacy. Recent evidence suggests that bacteria influence insect physiology and could be leveraged for pest management, but the postmortem microbial ecology of E. grisescens remains uncharacterized. In this study, we employed 16S rRNA sequencing to investigate temporal changes in the bacterial communities of E. grisescens cadavers at 0, 7, and 21 days following cryogenic mortality. Our results indicate a time-dependent decline in microbial diversity, while species richness initially increased before subsequent reduction. The dominant endosymbiont Wolbachia gradually diminished after host death, whereas Enterobacter remained abundant. Notably, non-dominant genera including Lysinibacillus and Sporosarcina exhibited a transient increase in abundance at day 7 before reverting to control levels by day 21. This study presents the first comprehensive analysis of postmortem microbial succession in a lepidopteran system, highlighting dynamic shifts in bacterial composition and offering potential avenues for microbiome-based pest management strategies. Full article

Background: Crimean–Congo hemorrhagic fever (CCHF) is a severe zoonotic viral infection with high mortality rates. This study aimed to examine the prognostic value of new-generation inflammatory markers—CRP/albumin ratio (CAR), D-dimer/albumin ratio (DAR), D-dimer/fibrinogen ratio (DFR), and triglyceride-glucose index (TGI)—in predicting mortality among patients diagnosed with CCHF. Methods: This prospective study involved 76 patients with a positive polymerase chain reaction test for CCHF and 38 age- and sex-matched healthy controls between 15 April 2023 and 15 October 2024. Participants’ demographic, clinical, and laboratory data at presentation were recorded. Results: CAR, DAR, DFR, and TGI levels were significantly higher in the patient group compared to the control group (all p < 0.001). Furthermore, when mortal cases were compared with survivors, all of these markers were found to be significantly higher in the mortal group (p = 0.005, p = 0.004, p = 0.001, and p = 0.003, respectively). In Kaplan–Meier analysis, survival time was significantly shorter in patients with higher levels of these parameters (p < 0.001 for all). In the Receiver Operating Characteristic analysis conducted to differentiate mortal cases from survivors, DFR and TGI were identified as the markers with the highest predictive power (area under the curve: 0.938 and 0.899, respectively). Conclusions: Inflammatory markers CAR, DAR, DFR and TGI may serve as significant prognostic tools to predict mortality in CCHF. Full article

Motivated by the recent CMS observation of a near-threshold enhancement in top quark pair production, we investigate a novel class of hadronic systems containing a single top quark: the topped mesons ($t\overline{q}$, with $\overline{q}=\overline{u},\overline{d},\overline{s}$). In contrast to the extensively studied toponium ($t\overline{t}$) system—analyzed primarily within perturbative QCD—topped mesons offer a complementary nonperturbative probe of QCD dynamics in the heavy quark limit. These states are expected to exhibit longer lifetimes and narrower decay widths than toponium, as only a single top quark undergoes weak decay. We employ QCD sum rules within the framework of heavy quark effective theory to study the structure and mass spectrum of ground-state topped mesons. Our analysis predicts masses near 173.1 GeV, approximately 0.5–0.6 GeV above the top quark pole mass. Compared with singly topped baryons ($tqq$, with $q=u,d,s$), topped mesons have a simpler quark composition and more favorable decay channels (a topped meson is anticipated to decay weakly into a ${\rm Y}$ meson and a charmed meson), enhancing their potential for both theoretical analysis and experimental discovery. Full article

Objectives: To identify factors correlated with post-surgery residue in cases of breast cancer incidentally found via vacuum-assisted excision (VAE). Methods: A total of 6083 patients were enrolled in a retrospective study. Ultrasound evaluation and ultrasound-guided VAE were performed on these patients. According to the pathology of VAE, 53 patients with incidentally found breast cancer were included in the final analysis. Either breast-conserving surgery or mastectomy was performed. The maximal diameter, depth, location, BIRADS category, and Adler’s grade of all lesions before VAE was reviewed and recorded. VAE and post-surgery pathologies were used as gold standards. Either Pearson’s chi-square test or Fisher’s exact test was used for comparison of categorical variables. Results: The mean age of the enrolled patients was 49 years (IQR: 43–55 years). The mean maximal diameter of the lesions was 11.3 mm (IQR: 7–15 mm). There were twenty-eight ductal carcinomas in situ, twelve invasive ductal carcinomas, five lobular carcinomas in situ, two invasive lobular carcinomas, four intraductal papillary carcinomas, and two mucinous carcinomas. Post-surgery pathology showed 15 cases with residual cancer and 38 cases with no residual cancer. The maximal diameter, depth, and pathology derived via VAE were statistically correlated with post-surgery residue (p < 0.05). Conclusions: Small incidentally found noninvasive carcinomas located comparatively deep in the breast could be totally excised by ultrasound-guided vacuum-assisted excision. Both large and superficially invasive carcinomas were more likely to be associated with residue. Full article

The induction of robust CD8 T cell immunity after intramuscular (i.m.) mRNA vaccination has remained a challenge. Due to the limited presence of professional antigen-presenting cells (APCs) in muscle tissue, this route of administration tends to result in the transfection of muscle cells at the injection site with insufficient T cell activation capacity. The attraction of migratory APCs and related processes that lead to the acquisition of antigenic material from transfected non-APCs arises as a potential alternative to facilitate activation of CD8 T cells in the draining lymph nodes. This indirect pathway, known as antigen cross-presentation, has remained underappreciated for mRNA vaccines. This review provides a comprehensive analysis of this process. Due to the paucity of information available in this context, it also extrapolates from insights for antigen cross-presentation more generally and for traditional vaccines. Arguments are provided as to why this natural process in the context of pro-drugs, such as mRNA vaccines, may engender both specific and nonspecific responses and, in certain situations, evoke cross-tolerance rather than immunity. This widely unaccounted T cell activation process may, therefore, explain several key mysteries surrounding i.m. RNA vaccination, including its impact on heterologous infections. But it also raises numerous open questions that are clearly described. Full article

Studies have shown that the iron concentration in the peritoneal fluid of women is associated with the severity of endometriosis. Therefore, investigation of iron metabolism-related genes (IM-RGs) in endometriosis holds significant implications for both prevention and therapeutic strategies in affected patients. Differentially expressed IM-RGs (DEIM-RGs) were identified by intersecting IM-RGs with differentially expressed genes derived from GSE86534. Mendelian randomization analysis was employed to determine DEIM-RGs causally associated with endometriosis, with subsequent verification through sensitivity analyses and the Steiger test. Biomarkers associated with IM-RGs in endometriosis were validated using expression data from GSE86534 and GSE105764. Functional annotation, regulatory network construction, and immunological profiling were conducted for these biomarkers. Single-cell RNA sequencing (scRNA-seq) (GSE213216) was utilized to identify distinctively expressed cellular subsets between endometriosis and controls. Experimental validation of biomarker expression was performed via reverse transcription–quantitative polymerase chain reaction (RT-qPCR). BMP6 and SLC48A1, biomarkers indicative of cellular BMP response, were influenced by a medicus variant mutation that inactivated PINK1 in complex I, concurrently enriched by both biomarkers. The lncRNA NEAT1 regulated BMP6 through hsa-mir-22-3p and hsa-mir-124-3p, while SLC48A1 was modulated by hsa-mir-423-5p, hsa-mir-19a-3p, and hsa-mir-19b-3p. Immune profiling revealed a negative correlation between BMP6 and monocytes, whereas SLC48A1 displayed a positive correlation with activated natural killer cells. scRNA-seq analysis identified macrophages and stromal stem cells as pivotal cellular components in endometriosis, exhibiting altered self-communication networks. RT-qPCR confirmed elevated expression of BMP6 and SLC48A1 in endometriosis samples relative to controls. Both BMP6 and SLC48A1 were consistently overexpressed in endometriosis, reinforcing their potential as biomarkers. Moreover, macrophages and stromal stem cells were delineated as key contributors. These findings provide novel insights into therapeutic and preventive approaches for patients with endometriosis. Full article

Background and Objectives: To evaluate the prognostic value of the Clinical–Pathologic Stage–Estrogen receptor status and Grade (CPS+EG) staging system, which combines clinical staging, pathological staging, oestrogen receptor (ER) status, and tumour grade in predicting survival outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant therapy (NACT). Materials and Methods: A retrospective review was performed on 245 female breast cancer patients who received anti-HER2 therapy alongside NACT at the Medical Oncology Department of Kartal Dr Lütfi Kırdar City Hospital, University of Health Sciences, from April 2012 to June 2024. The CPS+EG score was calculated using the MD Anderson Cancer Centre neoadjuvant treatment response calculator. Patients were categorised into two groups based on their CPS+EG score < 3 and ≥3. The primary outcomes assessed were disease-free survival (DFS) and overall survival (OS). Kaplan–Meier and log-rank tests were utilised for time-to-event analysis; Cox regression was used for multivariate analysis. A significance level of ≤0.05 was considered. Results: The median age of the patient cohort was 51 years (range: 27–82 years). Among these patients, 183 (74.6%) had a CPS+EG score less than 3, while 62 (25.3%) exhibited a score of 3 or higher. The median follow-up duration was 37.6 months. The pathological complete response (pCR) rate across the entire cohort was 51.8%. Specifically, the pCR rate was 56.3% in the group with CPS+EG scores below 3, and 38.7% in those with scores of 3 or higher (p = 0.017). Patients with CPS+EG scores less than 3 demonstrated superior overall survival (OS), which reached statistical significance in univariate analysis. Multivariate analysis identified the CPS+EG score as an independent prognostic factor for both overall survival and disease-free survival (DFS), with hazard ratios of 0.048 (95% CI: 0.004–0.577, p = 0.017) and 0.35 (95% CI: 0.14–0.86, p = 0.023), respectively. Conclusions: The CPS+EG score is an independent and practical prognostic marker, particularly for overall survival, in patients with HER2-positive breast cancer who have received neoadjuvant therapy. Patients with a CPS+EG score < 3 have higher pCR rates and survival rates. When used in conjunction with pCR, it can improve risk categorisation and contribute to the individualisation of adjuvant strategies in the post-neoadjuvant period. Due to its ease of calculation and lack of additional costs, this score can be instrumental in clinical practice for identifying high-risk patients. Our findings support the integration of the CPS+EG score into routine clinical decision-making processes, although prospective validation studies are necessary. Full article

Chronic sleep restriction (SR) impairs multiple organs. Although exogenous melatonin counteracts SR-induced gut microbiota disruption, its role in protecting renal function and the involvement of gut microbiota remain unclear. To this end, we subjected mice to a 28-day SR paradigm with exogenous melatonin treatment or antibiotic-induced microbiota depletion. SR mice demonstrated significant renal dysfunction evidenced by elevated serum creatinine, blood urea nitrogen, and uric acid levels compared to controls. Histopathological analysis revealed characteristic tubular abnormalities in SR mice, including epithelial degeneration and lumen dilation, with reduced expression of key renal filtration markers (Nephrin, Podocin, CD2-associated protein, and α-Actinin-4). All of these could be mitigated by melatonin treatment, and all changes were statistically significant (p < 0.05 or p < 0.01). Intriguingly, microbiota depletion significantly reversed the protective effect of exogenous melatonin on kidney injury in SR mice, while propionic acid supplementation mitigated SR-induced kidney injury. Furthermore, we found that gut microbiota and the metabolite propionic acid mediated the role of exogenous melatonin probably through attenuating SR-induced renal oxidative damage, including regulating renal superoxide dismutase (SOD) activity, total antioxidant capacity (T-AOC), and malondialdehyde (MDA) level. These findings collectively indicated that melatonin may ameliorate SR-associated kidney injury through gut microbiota-derived propionic acid. Our finding highlights a novel gut–kidney axis in SR-related pathophysiology. Full article

Growing consumer awareness of the link between diet and health has increased interest in functional foods, including fermented juices. Grapefruit juice has potential health-promoting properties, but its bitter taste limits its acceptance by consumers. This study aimed to develop a fermentation process for debittering grapefruit juice at natural pH using Lacticaseibacillus rhamnosus and naringinase. Grapefruit juice was fermented with Lactic. rhamnosus using free naringinase and naringinase immobilized on carob gum and chitosan supports at 30 ± 0.2 °C for 72 h. Naringin concentration, bacterial cell count, total phenol content, organic acids, carbohydrates, antioxidant activity, and pH were analyzed. Naringinase immobilized on carob gum demonstrated the highest efficiency, hydrolyzing over 42% of naringin after 24 h (from 418.20 to 241.19 μg/mL). The free enzyme reduced the naringin concentration to 155.28 μg/mL after 48 h. The highest Lactic. rhamnosus cell count (2.05 × 10⁹ CFU/mL) was achieved with the free enzyme. Total phenol content decreased from 42.24 to 16.58 mg GAE/100 mL when using naringinase immobilized on chitosan. The combined use of naringinase and Lactic. rhamnosus enables the development of an integrated process that improves consumer acceptance with potential applications in the functional beverage industry. Full article

‘Light-up’ aptamers are short oligonucleotides that can induce fluorescence of certain organic compounds upon binding. In this study, we compared three crystal violet (CV) aptamers—CV30S, parallel G-quadruplex (G4), and antiparallel G4—regarding their absolute fluorescence intensity, signal-to-background ratio (S/B), and potential as a core component in binary sensors for nucleic acid detection. The G4 antiparallel aptamer exhibited the highest fluorescence intensity and a robust S/B ratio, indicating its effectiveness in stabilizing the CV binding and enhancing fluorescence. In contrast, the G4 parallel aptamer demonstrated poorer performance, suggesting that its structural topology is less suitable for interactions with CV. The CV30S aptamer showed distinct advantages in binary sensor configurations, achieving the best limit of detection at 6 nM. Full article

Food industry generates substantial waste, raising economic and environmental concerns. Green Chemistry (GC) highlights the extraction of nutritional and bioactive compounds as a key strategy for waste valorization, driving interest in sustainable methods to recover valuable compounds efficiently. This review evaluates the sustainability of widely used emerging extraction technologies—Microwave-, Ultrasound- and Enzyme-Assisted, as well as Supercritical Fluid Extraction—and their alignment with GC principles for agri-food waste valorization. It first outlines the principles, key parameters, and main advantages and limitations of each technique. Subsequently, sustainability is then assessed in selected studies using the Analytical GREEnness Metric Approach (AGREEprep). By calculating the greenness score (GS), this metric quantifies the adherence of extraction processes to sustainability standards. The analysis reveals variations within the same extraction method, influenced by solvent choice and operating conditions, as well as differences across the techniques, highlighting the importance of process design in achieving green and efficient valorization. Full article

Anaxyelidae, a relict lineage of sawflies, are represented by a single extant species today but displayed remarkable Mesozoic diversity. Here, we describe the Orthosyntexis mascula sp. nov. from mid-Cretaceous Burmese amber. The new species can be readily distinguished by its forewing, with a normally sized, uniformly sclerotized pterostigma; 1-Rs shorter than 1-M; cell 1M more than twice as long as wide; absence of 1r-rs; 1-Cu, distinctly shorter than 2-Cu; 3-Cu shorter than 4-Cu; 2m-cu shorter than 1m-cu; and 3rs-m twice as short as 4-M. In the hind wing, abscissa 2-M+Cu present, 1-M shorter than 2-M, crossvein m-cu absent, and cell R1 closed. Mesotibia with two apical spurs. Examination of high-resolution photographs of Kempendaja jacutensis enables a revised interpretation of its venation, confirming its placement in Anaxyelinae. Comparative analysis of syntexine taxa further reveals that variation in the forewing crossvein 1r-rs consistently corresponds with hind wing venation, suggesting that multiple evolutionary trajectories may have existed within Syntexinae. These findings not only expand the known diversity of Cretaceous Anaxyelidae but also provide new evidence for reconstructing the evolutionary history and internal diversification of Anaxyelidae. Full article

Soil organic carbon (SOC) is a crucial indicator of soil quality and carbon cycling. While remote sensing and machine learning enable regional scale SOC prediction, most studies rely on vegetation indices (VIs) derived from bare-soil periods, potentially neglecting vegetation–soil interactions during crop growth. Given the bidirectional relationship between SOC and crop growth, we hypothesized that using crop-lush period VIs (VIs_lush) instead of bare-soil period VIs (VIs_bare) would increase the inversion accuracy. To test this hypothesis, we chose the cropland area in Liaoning Province as the study area and developed three modeling strategies (MS-1: VIs_lush + other features; MS-2: VIs_bare + other features; and MS-3: without VIs) using Landsat 8 imagery, topographic and precipitation data, and ensemble learning models (XGBoost, RF, and AdaBoost), with SHapley Additive exPlanations (SHAP) analysis for variable interpretation. We found that (1) all models achieved their highest performance under MS-1, with XGBoost outperforming the others across all modeling strategies; (2) for XGBoost, MS-1 yielded the highest inversion accuracy (R² = 0.84, RMSE = 2.22 g·kg⁻¹, RPD = 2.49, and RPIQ = 3.25); compared with MS-2, MS-1 reduced the RMSE by 0.31 g·kg⁻¹, increased R² from 0.77 to 0.84, and reduced the RPD by 0.31 and the RPIQ by 0.40, and compared with MS-3, MS-1 reduced the RMSE by 0.41 g·kg⁻¹, increased R² from 0.79 to 0.84, and reduced the RPD by 0.39 and the RPIQ by 0.51; (3) based on the SHAP analysis of the three modeling strategies, it is considered that precipitation, terrain and terrain analysis results are important indicators for SOC content inversion, and it is confirmed that VIs_lush contributed more than VIs_bare, supporting the rationale of using lush-period imagery; and (4) Liaoning Province exhibited distinct SOC spatial patterns (mean: 13.08 g·kg⁻¹), with values ranging from 2.19 g·kg⁻¹ (sandy central–western area) to 33.86 g·kg⁻¹ (eastern mountains/coast). This study demonstrates that integrating growth stage-specific VIs with ensemble learning can significantly enhance regional-scale SOC prediction. Full article