Search Results (681)

Polyglutamine expansion in Ataxin-2 (ATXN2) is responsible for rare, dominantly inherited Spinocerebellar Ataxia type 2 (SCA2). Together with its paralog Ataxin-2-like (ATXN2L), both proteins have received much interest, since the deletion of their yeast and fly orthologs alleviates TDP-43-triggered neurotoxicity in Amyotrophic Lateral Sclerosis models. Their typical structure across evolution combines LSm with LSm-Associated Domains and a PAM2 motif. To understand the physiological regulation and functions of Ataxin-2 homologs, the phylogenesis of sequences was analyzed. Human ATXN2 harbors multiple alternative start codons, e.g., from an intrinsically disordered sequence (IDR) present since armadillo, or from the polyQ sequence that arose since amphibians, or from the LSm domain since primitive eukaryotes. Multiple smaller isoforms also exist across the C-terminus. Therapeutic knockdown of polyQ expansions in human ATXN2 should selectively target exon 1B. PolyQ repeats developed repeatedly, usually framed and often interrupted by (poly)Pro, originally near PAM2. The LSmAD sequence appeared in algae as the characteristic Ataxin-2 feature with strong conservation. Frequently, Ataxin-2 has added domains, likely due to transcriptional readthrough of neighbor genes during cell stress. These chimerisms show enrichment of rRNA processing; nutrient store mobilization; membrane strengthening via lipid, protein, and glycosylated components; and cell protrusions. Thus, any mutation of Ataxin-2 has complex effects, also affecting membrane resilience. Full article

Background/Objectives: While excessive body fat is commonly linked to metabolic disorders (metabolically unhealthy obesity, MUO), a subset of individuals remain metabolic healthy despite obesity (metabolically healthy obesity, MHO). This work aims to determine how these phenotypes influence responses to lifestyle modification (LSM) in older adults. Methods: A 12-month lifestyle modification (LSM) intervention based on the Mediterranean Diet (MedDiet) and regular physical activity (PA) was conducted in 43 older adults (70% women) classified according to World Health Organization (WHO) criteria as MHO (22 subjects) or MUO (21 subjects). Clinical, dietary, and PA parameters were assessed at baseline and follow-up. Peripheral blood mononuclear cells were analyzed for mitochondrial fusion (OPA1, MFN2), mitophagy (PINK1), biogenesis (TFAM), and the respiratory chain (COX IV) using Western blot and RT-qPCR techniques. Results: At baseline, MUO showed significant lower OPA1-L, MFN2, and TFAM along with MFN2 degradation products and PINK1 accumulation. After 12 months of LSM, MUO participants exhibited greater metabolic profile improvements, such as significantly reduced MFN2 degradation products and higher COX IV. Changes in mitochondrial proteins were associated with nutrient intake and PA and clinical parameters with phenotype-specific patterns. In MUO, protein and cholesterol intake improved MFN2 fusion (rho = 0.446, p = 0.043; rho = 0.581, p = 0.006), while carbohydrates were negatively associated with OPA1 in MHO (rho = −0.596, p = 0.025). PA was positively related to fusion proteins in both phenotypes. Clinically, significant improvements in BMI, waist circumference, and HDL were found in MUO but not in MHO. Conclusions: Older adults with obesity show phenotype-specific mitochondrial impairments that shape distinct responses to LSM, highlighting the relevance of tailoring LSM interventions by metabolic phenotype. Full article

Rotating scanning systems are capable of acquiring ultra-wide swath satellite imagery, but they suffer from significant positioning accuracy degradation due to complex geometric distortions and the difficulty of obtaining ground control points (GCPs) over vast areas. To address these issues, this paper proposes a precise positioning method based on multi-source satellite data fusion. By comprehensively utilizing high-resolution images from ZY-3 and GF-2 satellites alongside DEM data, we establish a framework that integrates grid-based feature point extraction, high-precision matching, and multi-image joint adjustment. Specifically, we introduce a matching strategy combining geometric constraints with Least Squares Minimization (LSM) and a robust joint adjustment model to suppress geometric distortions. Experimental validation was conducted using a dataset covering the Beijing area. The results demonstrate that after joint adjustment, the planar accuracy of the imagery reached 4.01 m, and the edge matching Root Mean Square Error (RMSE) between adjacent images was 2.52 m. Furthermore, the cooperative positioning accuracy for segmented simulation data achieved 4.68 m in mountainous areas and 5.22 m in plain areas, meeting the requirements for meter-level positioning. These results verify the effectiveness of multi-source cooperative adjustment in correcting geometric distortions and significantly improving the positioning accuracy of rotating scanning imagery. Full article

Background/Objectives: Endoscopic variceal ligation (EVL) is a common treatment for preventing variceal bleeding in patients with advanced chronic liver disease (ACLD). However, its acute hemodynamic impact is typically assessed using invasive methods, and there is data on short-term spleen stiffness (SS) dynamics are limited. This pilot study aimed to quantify short-interval changes in liver stiffness (LS) and SS following EVL using transient elastography (TE), and to explore their associations with clinical and laboratory parameters. Methods: This prospective observational study enrolled adults with advanced liver disease undergoing esophagogastroduodenoscopy (EGD) with or without EVL at a tertiary center. Liver and spleen TE were performed in a fasted state immediately before endoscopy and repeated within 12 h after EVL. Organ-specific probes and predefined quality criteria were used, and non-parametric methods were applied to assess within-patient changes and correlations. Results: Fifty patients were included in the study: 21 underwent EVL, while the remaining 29 underwent diagnostic endoscopies only. The most common cause was alcohol-related liver disease. Within the EVL subgroup, the median liver stiffness (LSM) increased from 27.6 kPa to 45.1 kPa, and the median spleen stiffness (SSM) increased from 59.9 kPa to 98.3 kPa, both within 12 h. While these increases showed a uniform direction, they did not reach statistical significance. A higher baseline SS predicted a greater LS increase, and stiffness measures correlated with creatinine, disease duration, Child–Pugh class, albumin and ascites. Conclusions: Short-term increases in liver and spleen stiffness following EVL are consistent with acute hemodynamic alterations, such as increased hepatic perfusion and splenic congestion, rather than structural remodeling. These findings, beyond changes in stiffness alone, support the feasibility of integrating TE, particularly the measurement of SS, into early peri-procedural hemodynamic surveillance after EVL. They also justify larger studies with serial time points and direct portal pressure validation. Full article

Background: Persistent liver pathology despite a sustained virologic response (SVR) to hepatitis C virus (HCV) therapy is a major clinical concern. This is particularly relevant for people with HIV (PWH) with HCV coinfection, a population prone to accelerated liver disease progression. This study aimed to characterize the plasma miRNA profile in PWH with cirrhosis one year after successful completion of HCV therapy, and to explore their relationship with metabolite alterations. Methods: This cross-sectional study enrolled 47 PWH who achieved HCV clearance with antiviral therapy. Using plasma samples collected approximately one year after completion of HCV therapy, participants were stratified into two groups based on liver stiffness measurement (LSM): compensated cirrhosis (n = 32, LSM ≥ 12.5 kPa) and non-cirrhosis (n = 15, LSM < 12.5 kPa). Plasma miRNAs and metabolites were determined using small RNA sequencing and untargeted capillary electrophoresis-mass spectrometry (CE-MS), respectively. Significantly differentially expressed (SDE) miRNAs were identified using generalized linear models (GLM) with a negative binomial distribution, and their correlation with metabolite levels was quantified using Spearman’s correlation. Results: In the cirrhosis group (n = 32), we identified a distinct signature of 15 SDE miRNAs (9 upregulated, 6 downregulated) compared to the non-cirrhotic group (n = 15), showing hsa-miR-10401-3p, hsa-miR-548ak, hsa-miR-141-3p, and hsa-miR-3940-3p the largest expression changes. miRNA-gene interaction and pathway enrichment analysis suggested that these 15 SDE miRNAs potentially regulate multiple genes involved in immune response and amino acid metabolism. In addition, correlation analyses with our metabolomic data revealed significant associations between specific SDE miRNAs and amino acids and their derivatives. Specifically, the expression of upregulated miRNAs (e.g., hsa-miR-10401-3p and hsa-miR-16-5p) was positively correlated with plasma levels of L-methionine and its derivatives, while downregulated miRNAs (e.g., hsa-miR-625-5p) were inversely correlated with L-tryptophan. Conclusions: In cirrhotic PWH with history of HCV coinfection, a distinct plasma miRNA signature linked to dysregulated amino acid metabolism is found one year after completion of HCV therapy. This underscores that the HCV cure does not equate to complete hepatic recovery, highlighting the critical need for long-term monitoring in this high-risk population. Full article

Background/Objectives: We investigated the association between leisure-time physical activity (LTPA) and liver fibrosis, and whether this relationship differs by obesity and diabetes status. Methods: We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 2017–March 2020 cycle. LTPA was assessed using the Global Physical Activity Questionnaire (GPAQ) and classified as physically active if engaging in ≥600 metabolic equivalent (MET)-minutes per week of moderate-to-vigorous activity, or inactive. Clinically significant liver fibrosis was defined as liver stiffness measurement (LSM) ≥ 8.0 kPa on transient elastography. Multivariable logistic and linear regression models estimated adjusted odds ratios (ORs) for significant liver fibrosis, with additional subgroup analyses according to obesity and diabetes status. Results: In 7662 U.S. adults, physically active participants (n = 2721) had a lower prevalence of significant fibrosis than inactive individuals (5.4% vs. 11.4%, p < 0.001). In multivariable analysis, Participants who were physically active were associated with 42% lower odds of having fibrosis (OR 0.58, 95% confidence interval [CI] 0.41–0.82; p = 0.004). This association remained consistent in subgroup analyses stratified by obesity and diabetes status, even in the non-obese subgroup with body mass index (BMI) < 30 kg/m² (OR 0.54, 95% CI 0.32–0.91; p = 0.022) and the non-diabetic subgroup (OR 0.59, 95% CI 0.39–0.90; p = 0.016). Conclusions: Regular moderate-to-vigorous LTPA was independently associated with lower likelihood of clinically significant liver fibrosis. This beneficial association was significant regardless of obesity or diabetes status, suggesting that LTPA may play a clinically meaningful role in populations at high risk for progressive liver disease. Full article

Background/Objectives: Previous studies have demonstrated that the cessation of liver damage after HCV cure can improve liver function, histological necroinflammation, and portal hypertension. However, scarce data about fibrosis stage or cirrhosis regression have been reported during follow-up. Methods: A prospective study evaluating hepatic biopsies and liver stiffness measurement by vibration-controlled transient elastography (VCTE-LSM) after the end of treatment (EOT) in patients with compensated advanced chronic liver disease (cACLD). Fibrosis was evaluated according to two semi-quantitative grading systems (METAVIR and Laennec) at 6 years after EOT (LB6) and compared with biopsies at 3 years (LB3). Results: Fifty-four patients with LB6 (34 with paired LB3–LB6) were included. Median (IQR) age was 53.9 (48.5–59.3), 38 (70.4%) were men, and 13 (24.1%) were HIV-coinfected. The VCTE-LSM was >15 kPa in 30 (55.6%). The LB6 (81.4 months after EOT) showed non-advanced fibrosis (F1–F2) in 12 (22.4%) patients, bridging (F3) in 26 (48.2%), and cirrhosis (F4) in 16 (29.6%): F4A in 7 (13.0%), F4B in 4 (7.4%), and F4C in 5 (9.3%). The 1-year post-EOT follow-up VCTE-LSM ≤ 8.6 kPa identifies patients without advanced fibrosis (AUROC = 0.929), with a negative predictive value of 88.9% and a positive predictive value of 95.2%. Paired biopsies showed regression in 9 (47.4%) out of 19 patients with cirrhosis: 8 (61.5%) of 13 with F4A but only 1 (16.7%) of 6 with F4B–F4C. Conclusions: Advanced fibrosis persists in most patients with advanced chronic liver disease after HCV eradication. Regression is possible in mild cirrhosis. However, it is a limited and slow event. Full article

The budding yeast Saccharomyces cerevisiae has long served as a valuable model for investigating the molecular mechanisms underlying aging. Calorie restriction (CR) is a well-established intervention that extends lifespan across species, yet the underlying molecular mechanisms remain incompletely understood. In this study, we examined the effects of CR on the chronological lifespan, oxidative stress response, and autophagic activity of the Saccharomyces cerevisiae mutant Sclsm4Δ1, which exhibits premature aging and elevated reactive oxygen species (ROS) levels due to defects in mRNA decapping and processing-bodies (PB) dynamics. We found that both moderate (0.1% glucose) and extreme (water incubation) CR significantly extended the lifespan of Sclsm4Δ1 mutants and markedly reduced intracellular ROS accumulation without activating autophagy. These findings indicate that the beneficial effects of CR stem from improved redox homeostasis and metabolic adaptation, rather than from canonical autophagic pathways. Similar protective effects were observed in a chromosomal lsm4Δ1 mutant generated via CRISPR–Cas9, confirming that CR rescues aging-related phenotypes in different genetic backgrounds. These insights reinforce the roles of nutrient signaling, RNA metabolism, and redox balance in lifespan regulation, offering new perspectives on the conserved anti-aging effects of calorie restriction. Full article

Background: The transition from the term non-alcoholic fatty liver disease (NAFLD) to steatotic liver disease (SLD), an umbrella term for several related conditions, offers benefits, particularly in identifying cardiometabolic risk factors more effectively. However, the impact of alcohol consumption on liver disease progression remains significant, leading to the recognition of a new entity: MetALD (metabolic dysfunction-associated steatotic liver disease with moderate alcohol intake). Aim: This study aimed to compare characteristics associated with liver disease progression in diabetic patients diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD) versus those with MetALD. Materials and Methods: In this prospective study, 286 diabetic patients were followed for 12 months. All patients underwent transient elastography (TE) and ultrasound to assess hepatic steatosis. Participants were classified into MASLD and MetALD groups. The performance of fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) were also evaluated. Results: MASLD was diagnosed in 58.2% (167 patients), of whom 4.9% (7 patients) had TE values suggestive for liver cirrhosis. Among those with MetALD, 17.6% (21 patients) had TE values compatible with advanced fibrosis. MASLD subjects presented a slight decrease in liver fibrosis values from 6.58 ± 2.27 kPa to 6.03 ± 1.57 kPa in the 12 months. On the contrary, MetALD subjects had an increase of liver stiffness measurements (LSM) values from 11.83 ± 6.27 kPa to 12.24 ± 8.66 kPa. Conclusions: in diabetic patients, the coexistence of moderate alcohol intake and cardiometabolic risk factors (MetALD) is associated with more advanced liver fibrosis and impaired long-term glycemic control, compared to MASLD alone. Full article

Landslides are geological hazards that endanger socioeconomic development and ecological security, with landslide susceptibility mapping (LSM) playing a critical role in risk management and spatial planning. Recently, ensemble learning (EL) models have gained attention for effectively addressing the limitations of individual deep learning (DL) models in LSM. However, EL models always built on single-pixel, multi-factor inputs struggle to capture the spatial structure features of terrain units, limiting their ability to depict complex disaster patterns. Moreover, the scarcity of landslide samples and high annotation costs constrain model performance in LSM. To overcome these challenges, we propose a Stacking model based on multidimensional feature collaboration and pseudo-labeling techniques, referred to as MFP_Stacking. A stacking EL model is first employed in MFP_Stacking to integrate global statistical attribute features extracted from one-dimensional vectors with multi-scale spatial topological features derived from three-dimensional vectors. This strategy of multidimensional feature collaborative modeling enhances the model’s ability to learn complex environmental patterns associated with landslides. Subsequently, pseudo-labeling techniques are adopted to incorporate unlabeled data into auxiliary training, thereby addressing the problem of sample scarcity. MFP_Stacking was applied to LSM in the Zigui–Badong section of the Yangtze River Basin and in Ya’an City, Sichuan Province. Experimental results demonstrate that the proposed model performs well in overcoming limitations in feature representation, alleviating sample scarcity, and enhancing the quality of LSM outcomes. It achieved an average improvement of 2.4% for the Zigui–Badong section and 2% for Ya’an City across various evaluation metrics compared to other models. Full article

Zero-day intrusions on IoT endpoints demand defenses that curtail attacker impact and persistence after breach. This article presents Fine-Grained Runtime Containment Agent (FG-RCA), a lightweight post-exploitation containment system that learns least-privilege behavior from execution and enforces it in the kernel via eBPF with Linux Security Modules (LSM). In a learn phase, LSM/eBPF probes stream security-relevant events to a Rust agent that synthesizes policies per device role. In an enforce phase, policies are compiled into eBPF maps and evaluated at an extended hook set spanning process execution (bprm_check_security), file access (file_open), network egress and exfiltration (socket_connect, socket_sendmsg), privilege use (capable), process injection (ptrace_access_check), tamper/anti-forensics (inode_unlink). Policies bind to kernel-truth identities—inode, device, mount intrusion detection system (IDS), executable SHA-256, and cgroup/namespace identifiers—rather than paths, mitigating time-of-check to time-of-use (TOCTOU) and aliasing. Operational safeguards include Ed25519-signed policies, atomic rollback, and shadow mode logging events to enable policy evolution. Evaluation on embedded Linux demonstrates containment with low overhead. Full article

Sustainable management of cultural heritage in mountainous regions requires effective strategies to mitigate natural hazards such as landslides. Landslide susceptibility mapping (LSM) provides a critical tool to support these conservation efforts. This study presents a hybrid framework that integrates probabilistic slope stability modeling with ensemble learning for LSM in the UNESCO World Heritage sites of Shirakawa-gō and Gokayama, Japan. The framework uses probabilities of failure from Bishop’s simplified method combined with Monte Carlo simulations to guide non-landslide sample selection. An enhanced tri-parametric optimization was applied to refine the slope unit segmentation process. SHAP analysis revealed that the hybrid framework emphasizes physically meaningful features such as rainfall. The proposed method results in AUC gains of 0.072 for XGBoost, 0.066 CatBoost for, and 0.063 for LightGBM compared to their buffer-based counterparts. Future landslide susceptibility was mapped based on the 2035 precipitation projections from ARIMA time-series modeling. By enhancing accuracy, interpretability, and geotechnical consistency, the proposed approach delivers a robust tool for sustainable risk management. The study further evaluates the exposure of Gasshō-style houses and other historic buildings to varying levels of landslide susceptibility, offering actionable insights for local planning and heritage conservation. Full article

The Lushan Russet potato, cultivated in Lushan Mountain (China), is renowned for its unique flavor, which deteriorates when cultivated at low altitudes. To unravel its flavor determinants, we compared high/low-altitude-cultivated Lushan Russet potato (LsM/LS) and reference Zhongshu5 (Zs) via nutritional, metabolomic, and endophytic microbiota analyses. LsM/LS had higher dry matter, potassium, and other flavor-related components than Zs. Non-targeted LC-MS metabolomics identified 461 metabolites. Pairwise comparisons revealed 263 significant differential metabolites (SDMs) between LsM and Zs (205 more abundant in LsM), 240 between LS and Zs, and 237 between LsM and LS. KEGG enrichment showed that SDMs were mainly involved in metabolic pathways. High-throughput sequencing of endophytic microbiota showed clear beta diversity separation, which correlated with metabolomic changes. These results indicate that Lushan Russet potato’s unique flavor is jointly determined by nutrient/metabolite accumulation and endophytic microbiome diversity, providing a basis for optimizing its quality and mitigating flavor deterioration in low-altitude cultivation. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent in patients with type 2 diabetes (T2D), and advanced fibrosis is the strongest predictor of liver-related morbidity and mortality. Therefore, early noninvasive risk stratification is critical. While the Fibrosis-4 (FIB-4) index and vibration-controlled transient elastography (VCTE) are widely used, the newer FibroScan-AST (FAST) score has shown promise in detecting at-risk metabolic-associated steatohepatitis (MASH) with significant fibrosis. Evidence comparing the FAST and FIB-4 indices in Middle Eastern T2D populations remains limited. We compared the diagnostic performances of these models for advanced fibrosis in Saudi patients with T2D and MASLD. Methods: We conducted a retrospective analysis of 273 patients diagnosed with T2D and MASLD. All patients underwent VCTE. To identify advanced fibrosis, we used liver stiffness measurement (LSM) as a surrogate marker for liver biopsy. We calculated the FAST and FIB-4 indices for each patient. To assess the diagnostic performance of these scores, we evaluated their sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUROC). Results: In this cohort study, 26.4% of participants had a high-risk FAST score (>0.35; median: 0.13). Patients with high-risk FAST scores (>0.35) were younger, had higher BMIs, elevated liver enzyme levels, and poorer glycemic control than those in the lower-risk groups. High-risk FAST scores were strongly correlated with elevated LSM, FIB-4, and controlled attenuation parameter values (p < 0.001). The FAST score demonstrated better performance than the FIB-4 index in detecting advanced fibrosis. It showed higher accuracy (85.4% vs. 77.3%), sensitivity (82.0% vs. 48.0%), and negative predictive value (95.5% vs. 87.8%) while maintaining a similar specificity. The AUROC values were 0.936 (95% CI: 0.901–0.971) for the FAST score compared to 0.711 (95% CI: 0.625–0.797) for the FIB-4 index. Conclusions: The FAST score demonstrated better diagnostic accuracy than the FIB-4 index and identified patients with poor metabolic control and obesity as being at the highest risk among Saudi patients with T2D and MASLD. These findings support the integration of other elastography-based tests into stepwise fibrosis screening pathways for diabetic populations, potentially improving the early detection of advanced fibrosis and patient outcomes. Full article

What people consume for breakfast and why they do so have not been widely studied, especially in developing-economy countries. This study aimed to determine the breakfast food habits and their drivers of adults in South Africa, a multiethnic middle-income country. An online cross-sectional survey was conducted among 1000 representative consumers of moderate to higher living standard (Living Standard Measure [LSM] range ≥ 5). Data from 842 respondents (mean age 41 years, 51.7% females and 48.3% males) was analyzed. Of 21 different food types in descending order, the most frequently consumed were bread, ready-to-eat (RTE) cereals, fruits/nuts, high-fibre cereal, yoghurt, and leftovers, all consumed weekly by 42–65% of respondents. Principal component analysis revealed that three components had eigenvalues > 1 characterized as “On-the-go”, “Traditional”, and “Ready-to-eat and functional cereals”. They explained 49% of the data. Decision tree analysis revealed that, for example, Black respondents were more likely to consume foods in the “traditional” category. Quick-and-easy options, notably bread, RTE cereals, fruits/nuts, and leftovers, were dominant, especially among lower LSM respondents. Tasty and filling, and value for money, as exemplified by leftovers and vetkoek (fried dough), were important considerations, particularly among these respondents. These drivers can lead to unhealthy choices, a major concern in South Africa with its high level of diet-related diseases. This study, however, indicates that South African consumers, irrespective of age, ethnicity, and living standard, rated healthfulness and nutritional value highly as a benefit, the highest for choosing 13 of the 21 foods. Additionally, aspects of wellness, e.g., feeling energized/recharged, rated very highly. Thus, it is concluded that the opportunity exists to support consumer needs of nutrition and wellness together with affordability, taste, and satiety. Full article