Browse Articles

Altered fibroblast-like synoviocyte epigenetics is responsible for deficient NUB1 expression in rheumatoid arthritis

Abstract Neddylation is a post-translational modification suppressed by the endogenous inhibitor NUB1, and its dysregulation in rheumatoid arthritis (RA) promotes inflammation and NF-κB activation. NUB1 expression in RA and osteoarthritis (OA) synovium and mechanisms underlying defective NUB1 induction in RA fibroblast-like synoviocytes (FLS) were evaluated. NEDD8 and IL-6 protein expression was increased and NUB1 was reduced in RA synovium compared with OA tissue, with significant differences in the lining region that correlated with higher cytokine expression and NF-kB translocation. IL-1β–induced NUB1 induction was impaired in RA FLS at both the mRNA and protein levels. To evaluate the mechanism, we assessed mRNA stability using actinomycin D, examined the role of SNHG12 by siRNA knockdown, analyzed MAP kinase signaling, and measured NUB1 promoter activity with a luciferase reporter assay. None could explain the reduced induction observed in RA FLS. Treatment with the DNA methylation inhibitor 5-azacytidine and the histone methylation inhibitor EPZ6438 partially reversed the difference in NUB1 induction, whereas the histone deacetylase inhibitors ITF2375 and MS275 eliminated it. Therefore, defective NUB1 induction in RA FLS is related to the aberrant epigenetic landscape in RA FLS and is associated with increased neddylation and increased IL-6 expression in rheumatoid synovium. Overcoming increased neddylation in RA represents a novel therapeutic approach.

Divergent understandings in comparative oncology

A long-range LiDAR–camera extrinsic calibration method for rail transit

Evolution of Pliocene-Pleistocene tropical terrestrial Andean temperature amplification

The Pliocene is the most recent epoch in which the Earth warmed under atmospheric CO 2 levels similar to today (>400 ppm). The Pliocene then transitioned to the colder Pleistocene epoch, with the initiation of large-scale Northern Hemisphere glaciations. Although ocean temperature changes across these epochs are relatively well-known, quantitative estimates of the magnitude of land temperature change in the tropics are scarce. We provide a Plio-Quaternary quantitative air temperature record based on the distribution of bacterial branched glycerol dialkyl glycerol tetraethers (brGDGTs) preserved in sediments of the Funza-II core in the Sabana de Bogotá, Colombia (~4°N). Using a refined age model based on new U-Pb zircon dates from ash layers, and a novel mixed-source model that disentangles contributions from lake- and soil-derived brGDGTs, we show that warm Pliocene (3.8 to 2.58 Ma) temperatures were 4 . 8 - 1.4 + 1.8 °C warmer than the last ~800,000 y of the colder Pleistocene. The evolution of Pliocene-Pleistocene temperature in our record largely mirrors long-term tropical sea surface temperature (SST) cooling, highlighting the linkages between sea and land temperatures in the low latitudes via greenhouse-gas forcing. The median amplitude of Pliocene-Pleistocene cooling in the northern tropical Andes exceeds that predicted by theory, highlighting the importance of regional feedbacks including lapse rate adjustments and/or changes in Pacific SST gradients to the long-term evolution of Andean temperature. This first quantitative terrestrial temperature reconstruction within 5° of the equator over the past 3.8 My highlights that both regional and global processes must be considered when constraining uncertainties for future warming scenarios.

International survey on the management of colorectal trauma and alignment with current guidelines

Selective peroxynitrite-mediated protein nitration catalyzed by glyoxalase domain containing protein 4

Tyrosine nitration alters the structure, function, and cellular localization of proteins and is implicated in the pathology of multiple diseases [G. Ferrer-Sueta et al. , Chem. Rev. 118 , 1338–1408 (2018), H. Ischiropoulos, Arch. Biochem. Biophys. 356 , 1–11 (1998), I. Griswold-Prenner et al. , J. Biol. Chem. 299 , 105038–10554 (2023)]. Although protein nitration is assumed to proceed via nonspecific chemical mechanisms, it is highly selective, suggesting the possibility of enzymatic catalysis. Here, we showed that glyoxalase domain-containing protein 4 (GLOD4), a previously uncharacterized protein, is an enzyme that catalyzes selective protein nitration. A primary in vivo target for GLOD4-mediated nitration is alpha-synuclein (α-syn), which is central to the pathogenesis of Parkinson’s disease (PD) and related disorders. We document tyrosine nitration of α-syn by GLOD4 in vitro, in cells, and in a murine model of synuclein pathology. The data identified a function of GLOD4 and other structurally related proteins that catalyze the peroxynitrite-mediated selective protein tyrosine nitration. This enzymatic catalysis of nitration may unearth pathophysiological mechanisms and potential interventions in diseases such as PD, cancer, and autoimmunity.

Cost of illness of Mycoplasma genitalium in Australia: an incidence-based approach incorporating resistance-guided therapy

Early psychosocial deprivation alters the refinement of neural dynamics across adolescence

Adolescence is a crucial period for the refinement of neural circuits and cognitive skills. During this time, executive functions mature alongside pronounced structural changes in the brain, including reductions in synapse density. Computational models suggest that synaptic pruning enhances performance by stabilizing neural dynamics—deepening attractor basins and accelerating return to baseline after perturbation. Here, we tested these predictions using EEG data from the Bucharest Early Intervention Project, a randomized controlled trial of foster care as an alternative to institutionalized care. Trial-by-trial EEG residuals during a Flanker task were modeled as a linear dynamical system, and changes in eigenvalue magnitude were tracked across adolescence. Across all groups, eigenvalues decreased with age, consistent with maturation of recurrent computations. However, children with histories of institutional care exhibited consistently higher eigenvalues, suggesting delayed or disrupted refinement of the neural dynamics. Importantly, higher eigenvalues were associated with poorer behavioral performance on the task, linking altered neural dynamics to altered executive functions. These findings demonstrate that early deprivation leaves a lasting imprint on the developmental trajectory of neural dynamics, affecting the maturation of brain systems underlying cognitive control.

Effect of divergent residual feed intake on the fecal microbiota in fattening Hanwoo steers

Lead in archived hair documents a decline in lead exposure to humans since the establishment of the US Environmental Protection Agency

Lead (Pb) is well known to be toxic to humans. We use archived hair from individuals living along the Wasatch Front in Utah to evaluate changes in exposure to lead over the last 100 y. Current concentrations of lead in hair from this population average almost 100 times lower than before the establishment of the Environmental Protection Agency. This low level of lead exposure is likely due to the environmental regulations established by Environmental Protection Agency.

Antibacterial potential of endophytic Streptomyces spp. isolated from peanut (Arachis hypogaea) roots: bioactiveprofiling and molecular docking studies

Abstract The worldwide escalation of antimicrobial resistance (AMR) necessitates the search for new bioactive agents from natural sources. Consequently, this study investigates the antimicrobial activity of endophytic Streptomyces spp. Eighteen Streptomyces isolates were recovered from sixteen peanut root samples using nitrate starch agar at 30 °C for 7 days. Among these, two strains, Streptomyces rochei RSA1 and Streptomyces sp. RSA2, exhibited significant antibacterial activity against both Gram-positive ( Bacillus cereus and Staphylococcus aureus ) and Gram-negative ( Pseudomonas aeruginosa and Escherichia coli ) bacteria, compared with six standard antibiotics. Nine metabolic bioactive compounds were identified using GC-MS. However, two compounds2-(butylthio) pyrimidine-4,6(1 H,5 H)-dione and 2,4-di-tert-butylphenol were particularly prominent (> 96% abundance). Functional groups were confirmed via FT-IR spectra. Molecular docking and dynamics simulations with relevant bacterial protein targets (PDB ID: 6FJH, 1O9G, 1J5E, and 9QT5) revealed strong hydrogen bonding and electrostatic interactions, with S. rochei RSA1 forming the most stable complex. Overall, peanut-derived endophytic Streptomyces represent promising sources of bioactive antibacterial metabolites for combating multidrug-resistant infections.

Flagellar rotation comes full circle

Evaluation of electric vehicle performance using driving cycle clustering based on motor-inverter losses and efficiency

Abstract This paper introduces the methodology for evaluating electric vehicle (EV) performance by integrating motor and inverter efficiency analysis with total losses assessment across representative driving cycle simulations. The proposed methodology integrates finite element analysis (FEA) of the Interior Permanent Magnet Synchronous Motor (IPMSM) with comprehensive modeling of inverter power electronics to accurately assess power electro-mechanical and conversion losses under realistic operating conditions. By considering the joint influence of motor behavior and inverter dynamics, the methodology enables a more accurate evaluation of EV performance across diverse driving cycles, offering a deeper understanding of efficiency variations and loss distribution throughout real-world operation. Additionally, the methodology is designed to minimize computational complexity while maintaining high accuracy for performance evaluations. Three standard driving cycles the Federal Test Procedure (FTP), the Worldwide Harmonised Light Vehicle Test Procedure (WLTP), and the New European Driving Cycle (NEDC) were selected to capture diverse driving scenarios. Initially, motor performance was simulated across all operating points within these cycles. Subsequently, a clustering technique was applied to condense the dataset without compromising accuracy, enabling a direct comparison between full cycle and clustered simulations. The study also evaluates the influence of two inverter types, insulated-gate bipolar transistor (IGBT) and metal-oxide-semiconductor field-effect transistor (MOSFET), on motor efficiency and losses. A case study on a 48-slot IPMSM integrated into an EV system illustrates the approach. Results show that clustering significantly reduces computational time while preserving essential performance characteristics. Moreover, inverter modeling reveals notable differences in efficiency and power losses between IGBT and MOSFET-based systems. These findings highlight the necessity of integrating motor and power electronics modeling for comprehensive EV design.

Oxidizing pollutants can disrupt nestmate recognition in ants

Eusocial hymenoptera recognize nestmates based on colony-specific profiles of cuticular hydrocarbons (CHCs). While these profiles contain a variety of alkanes, the less abundant alkenes are crucial for nestmate recognition [F. R. Dani et al. , Chem. Senses 30 , 477–489 (2005)]. However, due to their carbon–carbon double bonds, alkenes can easily become degraded by oxidants. One of those oxidants, ozone, that usually reaches concentrations of 10 ppb in nonurban areas and ca 30 ppb in cities nowadays has been reported to often exceed 100 ppb in highly polluted regions, with levels above 200 ppb occasionally reported. Here, we show that short exposure to such elevated levels degrades alkenes in CHC profiles of all six investigated ant species and compromises nestmate recognition in five of them. Furthermore, a separate experiment with long-term exposure to such ozone levels corrupted brood care behavior within ant colonies, resulting in the death of larvae. The oxidizing pollutants like ozone have already been shown to corrupt interactions of flowers and their pollinators [B. Cook et al. , J. Chem. Biol. 46 , 987–996 (2020)] as well as sex pheromone communication in multiple species of flies [N. J. Jiang et al. , Nat. Commun. 14 (2023)]. Our data suggest that the detrimental effects of oxidant pollutants may be even more far-reaching by jeopardizing the functionality of eusocial colonies.

Facile fabrication of porous BixSy/Si photodetectors by one step laser ablation in liquid

Abstract In this study, facile bismuth sulfide (Bi x S y ) porous nanostructures (NSs) were synthesized by the liquid-based pulsed laser ablation (PLAL) method. The Bi x S y nanostructures were formed by laser ablation of the bismuth (Bi) target within 1 M of thiourea [SC (NH 2 ) 2 ] aqueous solution, along a fixed 400 laser pulses. The influence of laser fluence on the microstructural, morphological, chemical, optical, and electrical features of Bi x S y porous film has been systematically examined. X-ray diffraction (XRD) analysis confirmed that all synthesized Bi x S y nanoparticles (NPs) demonstrated a poly-crystalline nature along orthorhombic crystal orientation. As the fluence of laser amplified from 6.37 J/cm²/pulse to 15.92 J/cm²/pulse, the attained direct bandgap of Bi x S y reduced from 1.8 to 1.69 eV. Photoluminescence (PL) measurements showed a single emission peak at 672, 677, 712, and 729 nm for Bi x S y NSs prepared at 6.37, 9.55, 12.74, and 15.92 J/cm²/pulse, respectively. Raman spectroscopy revealed three vibrational modes positioned around 294, 510, and 654 cm⁻¹. Field emission scanning electron microscope (FE-SEM) images displayed the construction of a porous, grid-like nanostructure, with particle sizes ranging from 34.08 nm to 44.65 nm for sample fabricated with 15.92 J/cm²/pulse fluence. The dark I-V features of Al/n-Bi x S y /p-Si/Ag heterostructured photodetectors demonstrated rectifying behavior. Under incident light, the photo current-voltage (I-V) properties indicated high photosensitivity. A device attained at fluence of 12.74 J/cm²/pulse exhibited the highest responsivity (1.139 A/W) and specific detectivity (1.68 × 10 ¹³ Jones) at 375 nm. Additionally, the highest external quantum efficiency (EQE) of 376.52% was achieved at 375 nm for the same photodetector. The time-resolved analysis (ON/OFF states) are also demonstrated by means of laser fluence.

Development and investigation of the psychometric properties of the rehabilitation resilience scale (RRS) for caregivers of children with cerebral palsy

Noncircular rolling contact joints enable programmed behavior in robotic linkages

Rolling contact joints (RCJs) guide motion in robotic linkages, including manipulators, surgical devices, prosthetics, and more. In this work, we present a generalized optimization method to tailor the kinematic properties of RCJs by simultaneously optimizing both noncircular surface geometries and internal actuation pulley shapes. Our approach accommodates multiple joint types, including passively coupled systems with programmable spring stiffness as well as actuated single or multilink mechanisms. We explicitly incorporate common and practical manufacturing constraints into our optimization framework, such as size and convexity constraints. To demonstrate this approach, we optimize an RCJ designed to replicate the trajectory of a human knee, achieving a 99.6% reduction in alignment error compared to revolute joints and a 99.3% error reduction compared to circular RCJs. Additionally, we show that optimized RCJs increase the load-carrying capacity of a two-finger gripper by more than 3.5 times compared to a comparable circular-jointed design, showcasing how joint optimization can enhance robotic performance.

Nano-silicon enhances drought tolerance, yield stability, and bio-active compounds in Lallemantia iberica under water deficit conditions

Projecting nitrous oxide over the 21st century, uncertainty related to stratospheric loss

Extending the N 2 O lifetime derived from Microwave Limb Sounder satellite observations, we find a mean value of 117 y and a likely decrease of –1.4 ± 0.9% per decade over the period 2004 to 2024. This trend is consistent with the previously published 2004 to 2021 value of –2.1 ± 1.2% per decade. A more careful analysis of uncertainty now provides a more robust likely (one-sigma) range. From analyses of a range of factors controlling the N 2 O lifetime, we find that the decrease in lifetime can be explained by recent changes in stratospheric circulation and temperature. Projection of the lifetime change to 2100 shows that this effect is comparable to differences across the shared socioeconomic pathways used for climate projections and cannot be ignored. An updated evaluation of the N 2 O chemical feedbacks shows that this effect produces a relatively small shift in atmospheric abundance over the 21st century, but still an important shift, –11%, in the global warming potential of N 2 O.

Flood susceptibility assessment using three machine learning techniques and comparison of their performance

Abstract One of the most common natural disasters is flooding, which has the potential to seriously harm environments and infrastructure. Flood susceptibility mapping (FSM) is the main way to manage flood risk. It measures how likely a region is to flood in a quantitative way. The purpose of this study was to develop state-of-the-art ensemble machine learning (ML) models for flood prediction and to identify the most suitable approach for accurate flood susceptibility mapping. This study leverages diverse datasets, including elevation, slope, aspect, plan curvature, topographic wetness index, stream power index, distance from rivers, soil, rainfall, land use/land cover, and drainage density, which were used as conditioning factors to evaluate flood susceptibility in the Choke Watershed. Three machine learning (ML) algorithms were employed: Random Forest (RF), Gradient Boosting (GB), and Extreme Gradient Boosting (XGBoost). Model performance was assessed using confusion matrix metrics and the area under the receiver operating characteristic curve (AUROC). The Gradient Boosting (GB) and Extreme Gradient Boosting (XGBoost) models scored the highest in terms of test accuracy (0.97), followed by RF (0.96). This study is the first application of these models in the Choke Watershed for flood susceptibility mapping, with potential for broader applications to other natural disasters, including earthquakes and landslides. The results help strengthen global efforts aimed at mitigating natural disaster risks, particularly in Ethiopia, and advancing environmental sustainability.