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To investigate the factors associated with treatment outcomes of postcataract surgery fungal endophthalmitis outbreaks related to contaminated viscoelastics.

AbstractWe aimed to further explore the relationship between heterocyclic molecules and their associated biological activities for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. A dataset of 36 heterocycles was used to predict the activity of AChE and BChE inhibitors (the pIC50 values ranged from 7.84 to 12.49). A quantitative structure-activity relationship (QSAR) study was generated with the help of four different models (BMA, MNLR, MLR, and ANN). Four of the models were statistically acceptable based on both internal and external validation. The descriptors used in the models were similar to the X-ray structures of the target-ligand complexes, which made it possible to predict the pIC50 for AChE and BChE enzymes. Five selected molecules (compounds 6 (C21H21F3N4O), compound 7 (C22H23F3N4O), and compound 8 (C22H23F3N4O2) belong to the oxadiazole derivative group; compound 16 (C17H13ClN2O3) is classified into the chemical structures of different N, O, and S-based heterocycle groups; and compound 25 (C19H17NO2) pertains to the pyrimidine derivative group) possessed high pIC50 values for AChE and BChE enzymes (pIC50 values for AChE and BChE ranged from 9.01 to 10.32). The range of docking scores between the AChE and BChE receptors and their respective candidates was from −8.1 to −9.2 kcal/mol. The pharmacokinetics, biological activities, and physicochemical properties of five selected compounds supported their ability to protect against AD because they are not toxic, have a cholinergic effect, can cross the blood-brain barrier, and are well absorbed by the gastrointestinal tract.Communicated by Ramaswamy H. Sarma

Aerobic granular sludge (AGS) is a spherical aggregate formed by the self-aggregation of activated sludge. AGS consists of diverse microbial groups, not only shortening the settling time but also enhancing treatment efficacy within a shorter reaction time. However, it necessitates a longer start-up time for granule formation. This study aims to investigate the synergistic effects of powdered activated carbon (PAC) on AGS formation in a sequencing batch reactor (SBR) and its potential for maintaining biodegradability in the presence of inhibitory organic micro-pollutants (OMPs). PAC substantially supported the formation of faster and more stable granule (PAC-AGS) with a very low sludge volume index (SVI < 50 mL/g). Morphological observation indicated that PAC-AGS is more compact than AGS without PAC addition, and PACs were broadly present inside and on the surface of PAC-AGS granules. Respirometric bioassay demonstrated that biodegradation of organic matter in the presence of OMP, e.g., diclofenac and isoproturon, was enhanced when PAC-AGS was used as seed instead of AGS due to the alleviated inhibition of those OMPs by PAC. The overall result illustrated that PAC has dual positive contributions to AGS reactor for wastewater treatment by accelerating the formation of AGS and enhancing removal performance even in the presence of inhibitory OMPs.

SA508 Gr.1A low-alloy steel is being considered as a candidate material for main steam line piping in nuclear power plants. Therefore, improving its strength and toughness is essential for enhancing the leak-before-break (LBB) margin. In this study, six types of model alloys were fabricated by varying the contents of microalloying elements (C, Cu, B, Ti, and Nb) to enhance the mechanical properties of the specimens. The addition of a few ppm of B led to the formation of a fine-grained low-temperature transformation microstructure, resulting in the highest strength among the model alloys. However, the addition of Nb and Ti increased the formation of coarse ferrite, significantly decreasing the strength of the alloys. Reducing the C content while adding a small amount of B simultaneously maintained strength and enhanced toughness. Furthermore, the LBB margins of model alloys and commercial steel were evaluated to validate the influence of varying microalloying content. The model alloys exhibited a substantial increase in yield strength and fracture resistance, resulting in a more than 10% increase in the LBB margin. Notably, the LBB margin of the alloy with 15 ppm B was 1.39, approximately 25% higher than that of commercial steels.

Appendicitis is a common surgical emergency that poses a large clinical and economic burden. Understanding the global burden of appendicitis is crucial for evaluating unmet needs and implementing and scaling up intervention services to reduce adverse health outcomes. This study aims to provide a comprehensive assessment of the global, regional, and national burden of appendicitis, by age and sex, from 1990 to 2021.

We propose a hydrogel immobilized with manganese porphyrin (MnP), a biomimetic superoxide dismutase (SOD), and catalase (CAT) to modulate reactive oxygen species (ROS) and hypoxia that impede the repair of large bone defects. Our hydrogel synthesis involved thiolated chitosan and polyethylene glycol-maleimide conjugated with MnPs (MnP-PEG-MAL), which enabled in situgelation via a click reaction. Through optimization, a hydrogel with mechanical properties and catalytic effects favorable for bone repair was selected. Additionally, the hydrogel was incorporated with risedronate to induce synergistic effects of ROS scavenging, O2generation, and sustained drug release. In vitrostudies demonstrated enhanced proliferation and differentiation of MG-63 cells and suppressed proliferation and differentiation of RAW 264.7 cells in ROS-rich environments. In vivoevaluation of a calvarial bone defect model revealed that this multifunctional hydrogel facilitated significant bone regeneration. Therefore, the hydrogel proposed in this study is a promising strategy for addressing complex wound environments and promoting effective bone healing.

We demonstrate a high-performance and low-noise single-chip sub-terahertz (THz) imager array by integrating ground (gnd)-out trantenna (transistor-antenna) with a reset switch, analog buffer, multiplexer, and preamplifier using 65-nm CMOS technology. The channel charge asymmetry of sub-THz pixel device is enhanced with ac-gnd and ac-open load impedance design for gnd-out and gnd-in trantenna, respectively. The reset modulation switch suppresses output overshoot. Thus, the detector delay time of gnd-out trantenna, with a considerably smaller output junction capacitance than gnd-in trantenna, is reduced to sub- $\mu $ s regime. In 0.1-THz direct illumination setup, the gnd-out trantenna with analog buffer circuitry experimentally achieves high-speed sub-THz imager operation up to 600 kHz with a commercial-level delay time $= {0.98}~\mu $ s (15 times faster than gnd-in case). Owing to low-impedance analog buffer design for gnd-out trantenna with high-speed reset switch modulation ( ${\sim }{300}$ kHz), a high responsivity ( ${R}_{V} = {620}$ kV/W) and ultralow noise-equivalent power (NEP $= {8.44}$ pW/Hz0.5) are obtained for the peripheral circuitry-integrated sub-THz imager.

As research on in vitro cardiotoxicity assessment and cardiac disease modeling becomes more important, the demand for human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is increasing. However, it has been reported that differentiated hPSC-CMs are in a physiologically immature state compared to in vivo adult CMs. Since immaturity of hPSC-CMs can lead to poor drug response and loss of acquired heart disease modeling, various approaches have been attempted to promote maturation of CMs. Here, we confirm that peroxisome proliferator-activated receptor alpha (PPARα), one of the representative mechanisms of CM metabolism and cardioprotective effect also affects maturation of CMs. To upregulate PPARα expression, we treated hPSC-CMs with fenofibrate (Feno), a PPARα agonist used in clinical hyperlipidemia treatment, and demonstrated that the structure, mitochondria-mediated metabolism, and electrophysiology-based functions of hPSC-CMs were all mature. Furthermore, as a result of multi electrode array (MEA)-based cardiotoxicity evaluation between control and Feno groups according to treatment with arrhythmia-inducing drugs, drug response was similar in a dose-dependent manner. However, main parameters such as field potential duration, beat period, and spike amplitude were different between the 2 groups. Overall, these results emphasize that applying matured hPSC-CMs to the field of preclinical cardiotoxicity evaluation, which has become an essential procedure for new drug development, is necessary.Graphical Abstract

Somatic cells accumulate genomic alterations with age; however, our understanding of mitochondrial DNA (mtDNA) mosaicism remains limited. Here we investigated the genomes of 2,096 clones derived from three cell types across 31 donors, identifying 6,451 mtDNA variants with heteroplasmy levels of ≳0.3%. While the majority of these variants were unique to individual clones, suggesting stochastic acquisition with age, 409 variants (6%) were shared across multiple embryonic lineages, indicating their origin from heteroplasmy in fertilized eggs. The mutational spectrum exhibited replication-strand bias, implicating mtDNA replication as a major mutational process. We evaluated the mtDNA mutation rate (5.0 × 10−8per base pair) and a turnover frequency of 10–20 per year, which are fundamental components shaping the landscape of mtDNA mosaicism over a lifetime. The expansion of mtDNA-truncating mutations toward homoplasmy was substantially suppressed. Our findings provide comprehensive insights into the origins, dynamics and functional consequences of mtDNA mosaicism in human somatic cells.

Being overweight is a key modifiable risk factor for cardiovascular disease. However, the impact of longitudinal changes in body mass index (BMI) on the risk of out‐of‐hospital cardiac arrests (OHCA) remains unclear, especially among overweight populations. This nested case–control study utilized data from the Korean National Health Information Database between 2009 and 2018. A total of 23 453 OHCA patients, who underwent national health check‐ups within 1 and 2–4 years before OHCA occurrence, and 31 686 controls, who underwent similar national health check‐ups, were included. The study population was matched for sex, age and survival status. Conditional logistic regression was employed to analyse the odds ratios (ORs) and 95% confidence intervals (CIs) of each BMI per cent change in assessing the risk of OHCA occurrence within 1 year. A reverse J‐shaped association between BMI per cent change and OHCA risk was observed, even among overweight populations. Among the overweight populations, weight loss significantly increased OHCA risk, with ORs (95% CI) of 4.10 (3.23–5.20) for severe weight loss (BMI decrease > 15%), 2.72 (2.33–3.17) for moderate weight loss (BMI decrease 10–15%) and 1.46 (1.35–1.59) for mild weight loss (BMI decrease 5–10%). Conversely, mild weight gain (BMI increase 5–10%) did not significantly increase OHCA risk. The impact of weight changes on the occurrence of OHCA differed by sex, being more prominent in males. Significant weight changes within a 4‐year period increase the risk of OHCA with a reverse J‐shaped association, even among overweight and obese individuals. Maintaining a stable weight could be a reliable public health strategy irrespective of the weight status, particularly for males.

Electrochemical CO2reduction reaction (eCO2RR) over Cu-based catalysts is a promising approach for efficiently converting CO2into value-added chemicals and alternative fuels. However, achieving controllable product selectivity from eCO2RR remains challenging because of the difficulty in controlling the oxidation states of Cu against robust structural reconstructions during the eCO2RR. Herein, we report a novel strategy for tuning the oxidation states of Cu species and achieving eCO2RR product selectivity by adjusting the Cu content in CuMgAl-layered double hydroxide (LDH)-based catalysts. In this strategy, the highly stable Cu2+species in low-Cu-containing LDHs facilitated the strong adsorption of *CO intermediates and further hydrogenation into CH4. Conversely, the mixed Cu0/Cu+species in high-Cu-containing LDHs derived from the electroreduction during the eCO2RR accelerated C–C coupling reactions. This strategy to regulate Cu oxidation states using LDH nanostructures with low and high Cu molar ratios produced an excellent eCO2RR performance for CH4and C2+products, respectively.

In laser-based additive manufacturing (AM), porosity and unmelted metal powder are typically considered undesirable and harmful. Nevertheless in this work, precisely controlling laser parameters during printing can intentionally introduce controllable porosity, yielding a porous electrode with enhanced catalytic activity for the oxygen evolution reaction (OER). This study demonstrates that deliberate introduction of porosity, typically considered a defect, leads to improved gas molecule desorption, enhanced mass transfer, and increased catalytically active sites. The optimized P-93% electrode displays superior OER performance with an overpotential of 270 mV at 20 mA cm–2. Furthermore, it exhibits remarkable long-term stability, operating continuously for over 1000 h at 10 mA cm–2and more than 500 h at 500 mA cm–2. This study not only provides a straightforward and mass-producible method for efficient, binder-free OER catalysts but also, if optimized, underscores the potential of laser-based AM driven defect engineering as a promising strategy for industrial water splitting.

Producing high-quality joints between high-strength steel and aluminum alloy presents a challenge, yet it is crucial for manufacturing state-of-the-art lightweight. This study investigates self-piercing riveting (SPR) for joining high-strength steel to aluminum alloy panels. The experimental results for both steel-on-top (SOT) and steel-on-bottom (SOB) configurations are presented for a range of ultimate tensile strength (UTS) values of steel up to 1180 MPa. The findings show that the SOT configuration consistently produces high-quality joints, whereas the SOB configuration, especially with higher UTS steel panels, results in inadequate joints. To overcome the challenge of the SOB configuration, we propose a novel approach that uses reinforcing aluminum plates beneath the lap joints during the SPR process. The cross-sectional characteristics and mechanical performance of joints formed with varying thicknesses of reinforcing plates under both configurations are discussed. The results demonstrate that introducing the reinforcing plates in the SOB configuration effectively eliminates geometrical defects and ensures acceptable joint strength, even with high-strength steel.

The purpose of this article is to revisit the biomechanical concepts of Paul Rolland’s scholarship on bowing to provide a new framework of Rolland’s underlying bowing principles. First, we discuss how whole body movements help facilitate natural bowing, which can generate better tone efficiently from freedom of movement. Second, we attend to the movements of the bow arm, which can be conceptualized as the natural rotation of the arm. Third, we comment upon the concept of balance, concerning bow hold, leverage, and bow pressure while discussing the particulars of finger placement, its function in bowing, and balance and leverage in the bow arm. The concepts of whole body, movement, and balance should be considered in variable conditions considering the relationship between body parts and the whole. Also, the three biomechanical concepts are not independent or self-sufficient but correlated ideas. Not only do these ideas help with the acquisition of technical skills, but they also pave the way for a pleasing and natural tone quality as well as enhanced musical expression.

Graphical abstract:

ABSTRACTBackgroundThis study compared the pharmacokinetics (PK), immunogenicity, and safety of candidate tocilizumab biosimilar, CT-P47, administered via auto-injector (CT-P47 AI) or pre-filled syringe (CT-P47 PFS), in healthy Asian adults.Research design and methodsIn this phase I, multicenter, open-label study, participants were randomized 1:1 to receive a single 162 mg/0.9 mL dose of CT-P47 via AI or PFS. Primary endpoints were area under the concentration – time curve from time zero to infinity (AUC0–inf) and maximum serum concentration (Cmax). PK equivalence was determined if 90% confidence intervals (CIs) for the ratios of geometric least-squares means (gLSMs) were within the predefined 80–125% equivalence margin. Secondary PK parameters, immunogenicity, and safety outcomes were also assessed.ResultsOf 314 participants randomized (155 CT-P47 AI; 159 CT-P47 PFS), 310 received the study drug (153 CT-P47 AI; 157 CT-P47 PFS). Primary and secondary PK results, immunogenicity and safety were similar between groups. Ninety percent CIs for the ratio of gLSMs were within the predefined equivalence margin for AUC0–inf(85.87–102.94) and Cmax(82.98–98.16).ConclusionsPK equivalence between CT-P47 AI and CT-P47 PFS was demonstrated in healthy Asian adults, with comparable immunogenicity and safety between the two devices.Trial registrationClinicalTrials.gov: NCT05617183.

In this cohort study of 4300 asymptomatic community-dwelling Korean adults, we demonstrated a detailed interplay between clonal haematopoiesis of indeterminate potential (CHIP) and conventional risk factors in the development of atherosclerotic cardiovascular disease (ASCVD).The presence of CHIP significantly increased the risk of ASCVD in the general population, displaying a notable synergistic effect with high levels of LDL cholesterol.Analyses of serial coronary computed tomography angiography scans revealed that CHIP, in conjunction with high LDL cholesterol levels, may contribute to the promotion of ‘early’ stage in coronary atherosclerosis, providing new insights into CHIP-associated atherosclerosis in the primary prevention.Graphical Abstract

This research main objective was to evaluate a proliposomes (PLs) formulation for the enhancement of oral bioavailability of ginsenosides, using ginsenoside Rg3 (Rg3) as a marker.

A combined experiment and multiscale modeling approach was presented to correlate the mechanical properties of a roll-bonded AA1050/AA3004 bimetal clad sheet and constituents. The mechanical responses of the 2-ply AA1050/AA3004 and constituents were measured under various loading conditions. For the measurements, each constituent was separated from the clad sheet using electrical discharge machining and uniaxial tensile tests. Continuum-scale yield functions such as isotropic von Mises and anisotropic/non-quadratic Yld2000-2d were developed for the two constituents and the bimetal clad sheet. A grain-scale crystal plasticity finite element (CPFE) simulations were also performed incorporated with newly developed representative volume element considering measured microstructural attributes. These CPFE predictions were used to identify the anisotropy coefficients for Yld2000-2d. Using the identified yield functions, finite element modeling was followed in which the mechanical properties of each constituent sheet were addressed separately. This is a new approach developed in the current work and it enables a fundamental correlation between multilayered material and its constituents. The mechanical properties of the bimetal clad sheet under the uniaxial tensions were predicted using those of the constituents and compared with calculations based on known rule of mixture (ROM) approach. The two approaches well reproduced stress–strain curves and r–value evolutions. The two FE modeling approaches were also applied to an independent test (i.e., the limiting dome height). The predictions were in good agreement with the experimental data. Finally, the mechanical properties of the bimetal clad sheet and constituents were correlated, and proper modeling scheme for multilayered materials is proposed.