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Fossil evidence of orchid-like dust seeds in Myanmar amber featuring early angiosperm radiation
Author Correction: AIM2 in regulatory T cells restrains autoimmune diseases
Lightweight UNet with multi-module synergy and dual-domain attention for precise skin lesion segmentation
An efficient dimensionality reduction framework using metaheuristic optimization with deep learning models for amyotrophic lateral sclerosis disease progression prediction
Copula-based multivariate analysis of hydrological drought over jiabharali sub-basin of Brahmaputra River, India
A numerical study of the mechanical properties and rock bridge coalescence of discrete distribution jointed rock masses under uniaxial loading
Analysis of sit-ski alpine skiing trajectories based on an inverted pendulum model
Abstract This study analyzes sit-ski alpine skiing trajectories during gate-turning phases using an inverted pendulum model combined with an advanced kinematic testing system involving inertial sensors and drone video analysis. Data were collected from 11 elite sit-ski athletes during runs on a designated slope segment. The inertial sensor system showed static accuracy of 2° and an average deviation of 0.008 m, while drone video analysis had a mean relative error of 1.36% ± 0.94%. Analysis of 33 gate turns revealed a mean skiing distance of 13.61 ± 2.87 m and mean time of 0.88 ± 0.19 s, with significant positive correlation ( $$\:p$$ < 0.05) between single-gate skiing time ( $${\it\text{t}}_{\text{s}}$$ ) and the minimum distance ( $${\it\text{d}}_{\text{m}\text{i}\text{n}}$$ ) ( $$\:\rho\:$$ = 0.74, $$\:p$$ < 0.01) and lateral distance ( $${\it\text{d}}_{\text{l}\text{e}\text{v}}$$ ) ( $$\:\rho\:$$ = 0.73, $$\:p$$ = 0.01). Simulation with the inverted pendulum model yielded a COM trajectory length of 97.93 ± 2.31 m, 1.66 ± 3.61 m shorter than actual values ( $$\:p$$ = 0.16), and a simulated time of 6.36 ± 0.64 s, showing strong consistency (ICC = 0.85 for time, ICC = 0.45 for trajectory length). These results confirm that optimizing the balance of turning radius, speed, and distance reduces skiing time, supporting the model’s effectiveness in individualizing trajectory optimization for sit-ski alpine skiing.
Maltose metabolism in serum free CHO culture involves lysosomal acid α-glucosidase
Abstract Mammalian cells have been previously shown to utilize maltose as an energy source for long-term cell growth. To characterize maltose uptake and consumption in CHO-K1, we measured its intracellular concentrations over time and tracked the incorporation of C13-labelled disaccharides into TCA cycle intermediates. Lysosomal acid α-glucosidase (GAA) was identified to potentially be involved in the initial reaction of breaking the α(1 → 4)-glycosidic bond in maltose, releasing two glucose residues for energy metabolism. Using a GAA-KO CHO-K1 cell line, we showed that GAA is involved in CHO-K1 maltose metabolism. Transport of maltose in wild-type and GAA-KO CHO-K1 is concentration-dependent. The rate of maltose uptake for GAA-KO cells was also linear when extracellular maltose is between 0 to 40 g/L, and saturation in uptake kinetics was not observed over that concentration range.
Correlation between effective optical zone and higher-order aberrations in keratorefractive lenticule extraction and wavefront-guided laser in situ keratomileusis
DNA metabarcoding confirms Copsychus saularis, the common insectivorous species in oil palm plantations as biological control of ground-dwelling insect pests
The impact of servant leadership on employees taking charge behavior
Uncertainty quantification enables reliable deep learning for protein–ligand binding affinity prediction
Author Correction: A metallic p-wave magnet with commensurate spin helix
Enhancing media image style transfer with advanced StyleGAN2 architectures
Clouded by Smoke
Prime editing-installed suppressor tRNAs for disease-agnostic genome editing
Abstract Precise genome-editing technologies such as base editing 1,2 and prime editing 3 can correct most pathogenic gene variants, but their widespread clinical application is impeded by the need to develop new therapeutic agents for each mutation. For diseases that are caused by premature stop codons, suppressor tRNAs (sup-tRNAs) offer a more general strategy. Existing approaches to use sup-tRNAs therapeutically, however, require lifelong administration 4,5 or show modest potency, necessitating potentially toxic overexpression. Here we present prime editing-mediated readthrough of premature termination codons (PERT), a strategy to rescue nonsense mutations in a disease-agnostic manner by using prime editing to permanently convert a dispensable endogenous tRNA into an optimized sup-tRNA. Iterative screening of thousands of variants of all 418 human tRNAs identified tRNAs with the strongest sup-tRNA potential. We optimized prime editing agents to install an engineered sup-tRNA at a single genomic locus without overexpression and observed efficient readthrough of premature termination codons and protein rescue in human cell models of Batten disease, Tay–Sachs disease and cystic fibrosis. In vivo delivery of a single prime editor that converts an endogenous mouse tRNA into a sup-tRNA extensively rescued disease pathology in a model of Hurler syndrome. PERT did not induce detected readthrough of natural stop codons or cause significant transcriptomic or proteomic changes. Our findings suggest the potential of disease-agnostic therapeutic genome-editing approaches that require only a single composition of matter to treat diverse genetic diseases.
Bile metabolite palmitic acid augments the migration of gallbladder cancer cells through the ROS/NF-кB signaling pathway
Idiopathic Normal-Pressure Hydrocephalus
Association between dietary inflammatory index and sarcopenia development in Polish population
Abstract Chronic low-grade inflammation associated with nutritional deficits and physical inactivity plays a key role in development and progression of skeletal muscle diseases. The study was designed to assess the inflammatory status in relation to dietary inflammatory index (DII) in sarcopenia. One hundred twenty-one individuals aged 60–96 years were allocated into sarcopenia ( n = 38), probable sarcopenia ( n = 38) and non-sarcopenia ( n = 45) group based on the algorithm of the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). The isometric strength of hand grip was measured using a hand dynamometer KERN type MAP130 (Germany). Sarcopenia cut-off points for low muscle quantity were evaluated using the appendicular skeletal muscle mass (ASM kg) and appendicular skeletal muscle mass index (ASMI kg/m 2 ). Meanwhile, the 6-min walk test (6MWT) was used to assess the severity of sarcopenia. In the quantitative assessment of the daily food rations, a single 24-hour dietary recall was applied. The Dietary Inflammatory Index was used to assess the Energy-adjusted Dietary Inflammatory Index (E-DII). The optimal threshold value for studied individuals corresponded to 2.283 for E-DII (AUC = 0.734, specificity 75.6%, sensitivity 70.6%, p < 0.001), which indicates an increased risk of sarcopenia with high intakes of pro-inflammatory dietary components. Furthermore, E-DII correlated with gait speed (r s = − 0.502, p = 0.001) and the 6MWT (r s = − 0.496, p = 0.001) thereby confirming the assumption that nutritional frailty and poor physical performance enhance sarcopenia symptomology. For E-DII and inflammatory profile models, AUC measurements for E-DII + cfDNA (cell free DNA) (AUC = 0.805) were considered a good discrimination, and the evaluation was as acceptable for cytokines interleukin 1β (IL-1β), interleukin 6 (IL-6), tumour necrosis factor α (TNFα) and C-reactive protein (CRP) (0.7 < AUC < 0.8) i.e., it enabled sarcopenia diagnosis. The analysis of E-DII with cfDNA (Classifier Accuracy 79.7%, p = 0.001) showed a higher diagnostic utility in sarcopenia prediction then conventional inflammatory markers such as IL-1β, IL-6 and TNFα, which may have important implications in defining healthy or unhealthy ageing. The results demonstrate that high intake of pro-inflammatory dietary components and low physical fitness may be one of the factors that increase the progression of sarcopenia in older adults Polish population, and simultaneously indicate a potential target for nutrition interventions to counteract the pathophysiological effects of skeletal muscle ageing.