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We propose a soft electromagnetic sliding actuator that provides various planar motions to construct highly compliant actuation systems. The actuator is composed of a fully soft actuation base (stator) for generating electromagnetic and magnetic forces and a rigid neodymium magnet (slider) that slides on the actuation base. A parallel liquid-metal coil array in the stator is designed based on theoretical modeling and an optimization process to maximize the electromagnetic field density. The stretchable magnetic components in the stator allow the slider to retain its position stably without additional constraints. By incorporating an untethered structure in which the slider is mechanically decoupled from the stator, the actuator can be operated with reduced power consumption, attributed to the absence of a restoring force. The trajectory of the slider can be programmed by selectively applying the input current to the liquid-meal coil array, and the location of the slider can be estimated by measuring the change in inductance of each coil. Moreover, the proposed actuator demonstrates the capability of operating on curved surfaces through its physical compliance as well as on inclined surfaces thanks to the holding force generated by the magnetic components of the stator. Taking advantage of the unique characteristics of our actuator, robotic applications, including shape morphing systems and sensor-actuator integrated systems, are demonstrated.

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The purpose of this study was to investigate the potential of discoidal polymeric particles (DPPs) coated with macrophage membranes as a novel drug delivery system. The study aimed to determine whether these coated particles could reduce phagocytosis, and target specific organs, thereby enhancing drug delivery efficacy. In this study, discoidal polymeric particles (DPPs) were synthesized by a top-down fabrication method serving as the core drug delivery platform. The method involved the fusion of macrophage cell membrane vesicles with DPPs, resulting in macrophage membrane coated DPPs. This process aimed to translocate membrane proteins from macrophages onto the DPPs, rendering them structurally and functionally like host cells. The results of this study showed that macrophage membrane coated DPPs exhibited a threefold reduction in phagocytosis compared to bare DPPs. This reduction in phagocytosis indicated the potential of these coated DPPs to evade immune clearance. Time-lapse microscopy further illustrated the distinct interactions of macrophage membrane coated DPPs with immune cells. Biodistribution studies revealed that these coated particles displayed preferential accumulation in the lungs at early time points, followed by sustained accumulation in the liver. In conclusion, this study demonstrated that macrophage membrane coated DPPs represent a unique and promising strategy for drug delivery. These particles can mimic cell surfaces, reduce phagocytosis, and target specific organs. This opens exciting avenues for improving drug delivery efficacy in diverse therapeutic contexts. These findings advance our understanding of nanomedicine's potential in personalized therapies and targeted drug delivery strategies. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-024-00396-x.

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Background: KRAS is frequently mutated in the tumors of patients with metastatic colorectal cancer (mCRC) and thus represents a valid target for therapy. However, the strategies of targeting KRAS directly and targeting the downstream effector mitogen-activated protein kinase kinase (MEK) via monotherapies have shown limited efficacy. Thus, there is a strong need for novel, effective combination therapies to improve MEK-inhibitor efficacy in patients with KRAS -mutated mCRC. Objective: Our objective was to identify novel drug combinations that enhance MEK-inhibitor efficacy in patients with KRAS -mutated mCRC. Design: In this study, we performed unbiased high-throughput screening (HTS) to identify drugs that enhance the efficacy of MEK inhibitors in vitro , and we validated the efficacy of the drugs in vivo . Methods: HTS was performed using 3-dimensional CRC spheroids. Trametinib, the anchor drug, was probed with 2 clinically ready libraries of 252 drugs to identify effective drug combinations. The effects of the drug combinations on CRC cell proliferation and apoptosis were further validated using cell growth assays, flow cytometry, and biochemical assays. Proteomic and immunostaining studies were performed to determine the effects of the drugs on molecular signaling and cell division. The effects of the drug combinations were examined in vivo using CRC patient-derived xenografts. Results: HTS identified paclitaxel as being synergistic with trametinib. In vitro validation showed that, compared with monotherapies, this drug combination demonstrated strong inhibition of cell growth, reduced colony formation, and enhanced apoptosis in multiple KRAS -mutated CRC cell lines. Mechanistically, combining trametinib with paclitaxel led to alterations in signaling mediators that block cell cycle progression and increases in microtubule stability that resulted in significantly higher defects in the mitosis. Finally, the combination of trametinib with paclitaxel exhibited significant inhibition of tumor growth in several KRAS -mutant patient-derived xenograft mouse models. Conclusion: Our data provide evidence supporting clinical trials of trametinib with paclitaxel as a novel therapeutic option for patients with KRAS -mutated, metastatic CRC.

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BACKGROUND: Numerous studies have compared the efficacy of ustekinumab (UST) and anti-TNF agents [infliximab (IFX) or adalimumab(ADA)] in moderate to severe Crohn's disease (CD) patients. This study aims to compare the efficacy of UST, IFX, and ADA while differentiating between bio-naïve and bio-experienced patients, which is an underexplored aspect, particularly in Asia. METHODS: We conducted a retrospective multi-center study from 2012 to 2023, categorizing patients into bio-naïve and bio-experienced groups. We evaluated clinical remission rates after induction therapy and clinical outcomes, including CD-related hospitalization, intestinal resection, and drug discontinuation during maintenance therapy. RESULTS: Among the 214 bio-naïve CD patients, 60 received UST, 108 received IFX, and 46 received ADA. After 1:1 propensity score matching between UST and anti-TNF agents groups, 59 patients were analyzed in each group (45 in the IFX group and 14 in the ADA group). We found no significant differences in clinical remission rates (P = 0.071), CD-related hospitalization (P = 0.800), intestinal resection (P = 0.390), or drug discontinuation (P = 0.052) between the UST, IFX, and ADA groups in bio-naïve CD patients. In bio-experienced CD patients, with 35 in the UST group and 13 in the anti-TNF agents group, the UST group showed a lower risk of drug discontinuation (P = 0.004) than the anti-TNF agents group. CONCLUSIONS: This study suggests that UST, IFX, and ADA are equally effective in bio-naïve CD patients, while in bio-experienced patients, mostly with previous exposure to anti-TNF agents, UST may offer superior drug durability.

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The self-assembly of nematic molecules in microcompartments with unambiguously defined surface anchoring is well predictable and is likely to have a single stable topological structure. Here, in contrast, a confined nematic system comprising an array of microcompartments interconnected by channels is demonstrated, exhibiting diverse molecular assembly pathways leading to the formation of four types of topological structures and twelve different patterns randomly distributed. Intercompartment communication via channels plays a crucial role in the diversity of patterns and distributions. It determines the sizes and structures of domains separated by channel defects. The domain structure, which features a pathfinding algorithm and reverse tree structure, can be modelled by an isotropically directed bond percolation with additional restrictions. This system serves as a model for controlled randomness and restricted growth of networks, with potential applications in anticounterfeit protection as a physically unclonable function (PUF) with multiple-level communication protocols.

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Objective: Acute respiratory distress syndrome (ARDS) presents a global health challenge, characterized by significant morbidity and mortality. However, the role of natural killer T (NKT) cells in human ARDS remains poorly understood. Therefore, this study explored the numerical and functional status of NKT cells in patients with ARDS, examining their clinical relevance and interactions with macrophages and fibroblasts during various stages of the syndrome. Methods: Peripheral blood from 40 ARDS patients and 30 healthy controls was analyzed, with paired samples of peripheral blood and bronchoalveolar lavage fluid (BALF) from seven ARDS patients. We measured levels of NKT cells, cytokines, CD69, programmed death-1 (PD-1), and annexin-V using flow cytometry, and extracellular matrix (ECM) protein expression using real-time PCR. Results: ARDS patients exhibited decreased circulating NKT cells with elevated CD69 expression and enhanced IL-17 production. The reduction in NKT cells correlated with PaO2/FiO2 ratio, albumin, and C-reactive protein levels. Proliferative responses to α-galactosylceramide (α-GalCer) were impaired, and co-culturing NKT cells with monocytes or T cells from ARDS patients resulted in a reduced α-GalCer response. Increased and activated NKT cells in BALF induced proinflammatory cytokine release by macrophages and ECM protein expression in fibroblasts. Conclusion: ARDS is associated with a numerical deficiency but functional activation of circulating NKT cells, showing impaired responses to α-GalCer and altered interactions with immune cells. The increase in NKT cells within BALF suggests their role in inducing inflammation and remodeling/fibrosis, highlighting the potential of targeting NKT cells as a therapeutic approach for ARDS.

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BACKGROUND: Phlegm is prevalent symptom in patients with chronic obstructive pulmonary disease (COPD). Few studies have investigated the effectiveness of N-acetylcysteine (NAC) nebulizer therapy in COPD patients. We evaluated the effect of nebulized NAC on the improvement of phlegm symptom in COPD patients. METHODS: This was a 12-week, prospective, single-arm, open-label, phase IV multi-center trial (NCT05102305, Registration Date: 20-October-2021). We enrolled patients aged ≥ 40 years with post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) < 0.7 and COPD assessment test (CAT) phlegm score ≥ 2; the patients were current or ex-smoker with smoking pack-years ≥ 10. The primary endpoint was to determine the change in CAT phlegm score at 12 weeks compared to the baseline. Patients were assessed at baseline, 4, 8, and 12 weeks of treatment using the CAT score. RESULTS: In total, 100 COPD patients were enrolled from 10 hospitals. The mean age of the patients was 71.42 ± 8.20 years, with 19.78% being current-smokers and 80.22% being ex-smokers. The mean smoking pack-years was 40.32 ± 35.18. The mean FVC, FEV1, and FEV1/FVC were 3.94 L (75.44%), 2.22 L (58.50%), and 0.53, respectively. The CAT phlegm score at baseline was 3.47 ± 1.06, whereas after 12 weeks of nebulized NAC it significantly decreased to 2.62 ± 1.30 (p < 0.01). More than half (53.5%) of the patients expressed satisfaction with the effects of nebulized NAC therapy. Adverse events occurred in 8 (8.0%) patients. Notably, no serious adverse drug reactions were reported. CONCLUSION: In this study, we have established the effectiveness and safety of nebulized NAC over 12 weeks.

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Phthalates are ubiquitous in diverse environments and have been linked to a myriad of detrimental health outcomes. However, the association between phthalate exposure and allergic rhinitis (AR) remains unclear. To address this knowledge gap, we conducted a systematic review and meta-analysis to comprehensively evaluate the relationship between phthalate exposure and childhood AR risk. We searched the Cumulative Index to Nursing and Allied Health Literature, Excerpta Medica Database, and PubMed to collect relevant studies and estimated pooled odds ratios (OR) and 95% confidence intervals (CI) for risk estimation. Ultimately, 18 articles, including seven cross-sectional, seven case-control, and four prospective cohort studies, were selected for our systematic review and meta-analysis. Our pooled data revealed a significant association between di-2-ethylhexyl phthalate (DEHP) exposure in children's urine and AR risk (OR = 1.188; 95% CI = 1.016-1.389). Additionally, prenatal exposure to combined phthalates and their metabolites in maternal urine was significantly associated with the risk of childhood AR (OR = 1.041; 95% CI = 1.003-1.081), although specific types of phthalates and their metabolites were not significant. Furthermore, we examined environmental phthalate exposure in household dust and found no significant association with AR risk (OR = 1.021; 95% CI = 0.980-1.065). Our findings underscore the potential hazardous effects of phthalates on childhood AR and offer valuable insights into its pathogenesis and prevention.

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Typically used household chemicals comprise numerous compounds. Determining mixture toxicity, as observed when using household chemicals containing multiple substances, is of considerable importance from a regulatory perspective. Upon examining the toxic effects of household chemical mixtures, we observed that hydramethylnon combined with tetramethrin resulted in synergistic toxicity. To determine the unknown toxicity mechanism of hydramethylnon, which carries the risk of inhalation exposure when using household chemicals, we conducted a further investigation using BEAS-2B cells, a human bronchial epithelial cell line. Hydramethylnon-induced cytotoxicity was determined following 24 and 48 h of exposure using the water-soluble tetrazolium 1 and lactate dehydrogenase assays. To elucidate the toxicity mechanism, we utilized flow cytometry and measured the levels of apoptosis-related proteins and caspase activities. Given that hydramethylnon, as an insecticide, disrupts the mitochondrial electron transfer chain, we analyzed the relevant mechanisms, including mitochondrial superoxide levels as well as the mitochondrial membrane potential (MMP). Hydramethylnon dose-dependently induced BEAS-2B cell apoptosis via the intrinsic pathway. Furthermore, it significantly increased mitochondrial superoxide levels and disrupted the MMP. Pre-treatment with a caspase inhibitor (Z-DEVD-FMK) confirmed that hydramethylnon induced caspase-dependent apoptosis. Apoptosis, a key event in the toxicological process of chemicals, can lead to lung diseases, including fibrosis and cancer. The results of the present study suggest a mechanism of toxicity of hydramethrylnon, an organofluorine biocide whose toxicity has been little studied, to the lung epithelium. Considering the potential risks associated with inhalation exposure, these results highlight the need for careful management and regulation of hydramethylnon.

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Current human risk assessments often rely on animal toxicity data to establish point of departure (POD) values, followed by the application of uncertainty factors. Consequently, there is growing interest in alternative toxicity testing methods that reduce reliance on animal models. In this study, we propose a novel approach for inhalation toxicity risk assessment that integrates in silico and in vitro methods. Human primary alveolar epithelial cells were exposed to aerosolized didecyldimethylammonium chloride (DDAC) to assess cytotoxicity. This was followed by transcriptome analysis and biological pathway investigation, utilizing adverse outcome pathway (AOP), to calculate the POD. Additionally, human DDAC exposure was simulated using a multiple-path particle dosimetry (MPPD) model to predict exposure levels in the human alveolar region via inhalation. The results from in silico and in vitro studies were then compared, and a comprehensive risk assessment was performed. The POD for AOP 452 key events-oxidative stress, inflammation, epithelial-mesenchymal transition (EMT), apoptosis, and autophagy-was found to range between 19.0 and 23.89 ng/cm2, according to benchmark dose calculation tools. The estimated human exposure to DDAC in the alveolar region under actual exposure conditions was 0.164 ng/cm2/day, resulting in a margin of exposure (MOE) ranging from 121 to 145, suggesting caution regarding DDAC inhalation exposure. This study presents a novel risk assessment method that compares estimated human inhalation exposure values to in vitro results, applying the human equivalent concentration concept. Our findings demonstrate the potential for conducting human risk assessments using both in silico and in vitro methods as alternatives to traditional in vivo studies.

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BACKGROUND: Medical therapy for aortic stenosis (AS) remains an elusive goal. OBJECTIVES: This study sought to establish whether evogliptin, a dipeptidyl peptidase-4 inhibitor, could reduce AS progression. METHODS: A total of 228 patients (age 67 ± 11 years; 33% women) with AS were randomly assigned to receive placebo (n = 75), evogliptin 5 mg (n = 77), or evogliptin 10 mg (n = 76). The primary endpoint was the 96-week change in aortic valve calcium volume (AVCV) on computed tomography. Secondary endpoints included the 48-week change in active calcification volume measured using 18F-sodium fluoride positron emission tomography (18F-NaF PET). RESULTS: There were no significant differences in the 96-week changes in AVCV between evogliptin 5 mg and placebo (-5.27; 95% CI: -55.36 to 44.82; P = 0.84) or evogliptin 10 mg and placebo (-18.83; 95% CI: -32.43 to 70.10; P = 0.47). In the placebo group, the increase in AVCV between 48 weeks and 96 weeks was higher than that between baseline and 48 weeks (136 mm3; 95% CI: 108-163 vs 102 mm3; 95% CI: 75-129; P = 0.0485). This increasing trend in the second half of the study was suppressed in both evogliptin groups. The 48-week change in active calcification volume on 18F-NaF PET was significantly lower in both the evogliptin 5 mg (-1,325.6; 95% CI: -2,285.9 to -365.4; P = 0.008) and 10-mg groups (-1,582.2; 95% CI: -2,610.8 to -553.5; P = 0.0038) compared with the placebo group. CONCLUSIONS: This exploratory study did not demonstrate the protective effect of evogliptin on AV calcification. Favorable 18F-NaF PET results and possible suppression of aortic valve calcification with longer medication use in the evogliptin groups suggest the need for larger confirmatory trials. (A Multicenter, Double-blind, Placebo-controlled, Stratified-randomized, Parallel, Therapeutic Exploratory Clinical Study to Evaluate the Efficacy and Safety of DA-1229 in Patients With Calcific Aortic Valve Disease; NCT04055883).

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INTRODUCTION: Muscle strength is known to play an important role in the health of older adults. The health burden of cigarette smoking among older adults remains significant. We investigated the association between smoking cessation and dynapenia among older lifetime smokers in Korea. METHODS: This study is a secondary dataset analysis of cross-sectional data from theKorea National Health and Nutrition Examination Survey (KNHANES) 2016- 2019. We included 1450 participants aged 65-79 years, excluding those who had never smoked. Dynapenia was defined as grip strength <28 kg for men and <18 kg for women based on the Asian Working Group for Sarcopenia 2019 criteria. Multivariable logistic regression analysis evaluated the association between smoking cessation and dynapenia. RESULTS: Compared with current smokers, the adjusted odds ratio (AOR) of dynapenia in former smokers was 0.66 (95% CI: 0.44-0.99). The AORs for smoking cessation periods of ≤10 years, 10-20 years, 20-30 years, and >30 years were 0.67 (95% CI: 0.39-1.16), 0.61 (95% CI: 0.36-1.03), 0.65 (95% CI: 0.37-1.14), and 0.52 (95% CI: 0.25-1.06), respectively. The AOR for dynapenia significantly decreased with the years since smoking cessation (p for trend=0.043). CONCLUSIONS: Our findings suggest that smoking cessation can reduce the likelihood of dynapenia among older lifetime smokers, with a decreasing likelihood trend associated with longer cessation periods.

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The NACHT-, leucine-rich-repeat-, and pyrin domain-containing protein 3 (NLRP3) is a critical intracellular sensor of the innate immune system that detects various pathogen- and danger-associated molecular patterns, leading to the assembly of the NLRP3 inflammasome and release of interleukin (IL) 1ß and IL-18. However, the abnormal activation of the NLRP3 inflammasome has been implicated in the pathogenesis of autoinflammatory diseases such as cryopyrin-associated autoinflammatory syndromes (CAPS) and common diseases such as Alzheimer's disease and asthma. Recent studies have revealed that pyrin functions as an indirect sensor, similar to the plant guard system, and is regulated by binding to inhibitory 14-3-3 proteins. Upon activation, pyrin transitions to its active form. NLRP3 is predicted to follow a similar regulatory mechanism and maintain its inactive form in the cage model, as it also acts as an indirect sensor. Additionally, newly developed NLRP3 inhibitors have been found to inhibit NLRP3 activity by stabilizing its inactive form. Most studies and reviews on NLRP3 have focused on the activation of the NLRP3 inflammasome. This review highlights the molecular mechanisms that regulate NLRP3 in its resting state, and discusses how targeting this inhibitory mechanism can lead to novel therapeutic strategies for NLRP3-related diseases.

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OBJECTIVES: Recently, a joint group of the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) proposed new criteria for Takayasu arteritis (TAK) (the 2022 ACR/EULAR criteria). This study applied the 2022 ACR/EULAR criteria to patients with previously diagnosed TAK based on the 1990 ACR criteria and investigated the concordance rate between the two criteria according to the four imaging modalities. METHODS: This study reviewed the medical records of 179 patients who met the 1990 ACR criteria for TAK. The imaging modalities included conventional angiography, computed tomography angiography, fluorodeoxyglucose-positron emission tomography, and magnetic resonance angiography. RESULTS: Regardless of the imaging modalities, the concordance rate between the two criteria was 85.5% when including all patients, whereas it increased to 98.1% when only patients aged ≤60 years were included. Among the four imaging modalities, computed tomography angiography exhibited the highest concordance rate between the two criteria (85.6%). The concordance rate among patients aged >60 years was 95.7%. Only one patient aged 50-60 years was reclassified as having both TAK and giant cell arteritis. CONCLUSIONS: The concordance rate was 85.5% regardless of the imaging modalities and increased to 86.9% on simultaneous computed tomography angiography and fluorodeoxyglucose-positron emission tomography imaging.

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BACKGROUND: Chronic hepatitis B virus (HBV) infection affects around 250 million people worldwide, causing approximately 887,000 deaths annually, primarily owing to cirrhosis and hepatocellular carcinoma (HCC). The current approved treatments for chronic HBV infection, such as interferon and nucleos(t)ide analogs, have certain limitations as they cannot completely eradicate covalently closed circular DNA (cccDNA). Considering that HBV replication relies on host transcription factors, focusing on host factors in the HBV genome may provide insights into new therapeutic targets against HBV. Therefore, understanding the mechanisms underlying viral persistence and hepatocyte pathogenesis, along with the associated host factors, is crucial. In this study, we investigated novel therapeutic targets for HBV infection by identifying gene and pathway networks involved in HBV replication in primary human hepatocytes (PHHs). Importantly, our study utilized cultured primary hepatocytes, allowing transcriptomic profiling in a biologically relevant context and enabling the investigation of early HBV-mediated effects. METHODS: PHHs were infected with HBV virion particles derived from HepAD38 cells at 80 HBV genome equivalents per cell (Geq/cell). For transcriptomic sequencing, PHHs were harvested 1, 2-, 3-, 5-, and 7 days post-infection (dpi). After preparing the libraries, clustering and sequencing were conducted to generate RNA-sequencing data. This data was processed using Bioinformatics tools and software to analyze DEGs and obtain statistically significant results. Furthermore, qRT-PCR was performed to validate the RNA-sequencing results, ensuring consistent findings. RESULTS: We observed significant alterations in the expression patterns of 149 genes from days 1 to 7 following HBV infection (R2 > 0.7, q < 0.05). Functional analysis of these genes identified RNA-binding proteins involved in mRNA metabolism and the regulation of alternative splicing during HBV infection. Results from qRT-PCR experiments and the analysis of two validation datasets suggest that RBM14 and RPL28 may serve as potential biomarkers for HBV-associated HCC. CONCLUSIONS: Transcriptome analysis of gene expression changes during HBV infection in PHHs provided valuable insights into chronic HBV infection. Additionally, understanding the functional involvement of host factor networks in the molecular mechanisms of HBV replication and transcription may facilitate the development of novel strategies for HBV treatment.

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Background and Objectives: This study investigated whether serum alpha-1-acid glycoprotein (AGP) at diagnosis could reflect the cross-sectional activity represented by the Birmingham vasculitis activity score (BVAS) and further predict poor outcomes during follow-up in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Materials and Methods: This study included 70 patients with AAV. Clinical data at diagnosis, including AAV-specific indices and acute-phase reactants such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), were reviewed. All-cause mortality, relapse, end-stage kidney disease (ESKD), cerebrovascular accident, and acute coronary syndrome were evaluated as poor outcomes of AAV. Serum AGP was measured using the sera obtained and stored at diagnosis. Results: The median age of the patients was 63.0 years, with 29 male and 41 female patients. The median serum AGP was 150.9 µg/mL. At diagnosis, serum AGP was significantly correlated with BVAS and ESR but not CRP or serum albumin. Additionally, serum AGP showed significant correlations with the sum scores of ear-nose-throat and pulmonary manifestations; however, no significant differences in serum AGP according to each poor outcome were observed. Although serum AGP at diagnosis tended to be associated with ESKD occurrence during follow-up, serum AGP at AAV diagnosis was not significantly useful in predicting the future occurrence of poor outcomes of AAV during follow-up. Conclusions: In this study, we demonstrated the clinical utility of serum AGP at AAV diagnosis in assessing the cross-sectional activity represented by BVAS in patients with AAV for the first time.

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Optimal timing of revascularization for patients who presented with non-ST segment elevation myocardial infarction (NSTEMI) and severe left ventricular (LV) dysfunction is unclear. A total of 386 NSTEMI patients with severe LV dysfunction from the nationwide, multicenter, and prospective Korea Acute Myocardial Infarction Registry V (KAMIR-V) were enrolled. Severe LV dysfunction was defined as LV ejection fraction ≤ 35%. Patients with cardiogenic shock were excluded. Patients were stratified into two groups: PCI within 24 hours (early invasive group) and PCI over 24 hours (selective invasive group). Primary endpoint was major adverse cardiac and cerebrovascular events (MACCE) including all-cause death, non-fatal MI, repeat revascularization, and stroke at 12 months after index procedure. Early invasive group showed higher incidence of in-hospital death (9.4% vs 3.3%, P = .036) and cardiogenic shock (11.5% vs 4.6%, P = .030) after PCI. Early invasive group also showed higher maximum troponin I level during admission (27.7 ±â€…44.8 ng/mL vs 14.9 ±â€…24.6 ng/mL, P = .001), compared with the selective invasive group. Early invasive group had an increased risk of 12-month MACCE, compared with selective invasive group (25.6% vs 17.1%; adjusted HR = 2.10, 95% CI 1.17-3.77, P = .006). Among NSTEMI patients with severe LV dysfunction, the early invasive strategy did not improve the clinical outcomes. This data supports that an individualized approach may benefit high-risk NSTEMI patients rather than a routine invasive approach.

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Cesium lanthanide chloride (Cs3LnCl6), a recently developed class of lanthanide-based zero-dimensional metal halides, has garnered a significant amount of interest because of its potential applications in scintillators, light-emitting diodes, and photodetectors. Although cesium lanthanide chloride demonstrates exceptional scintillator properties, conventional synthesis methods involving solid-state and solution-phase techniques are complex and limited on the reaction scale. This study presents a facile mechanochemical synthesis method for producing Cs3CeCl6, Cs3TbCl6, and Cs3EuCl6 metal halides on a 5 g scale. These materials exhibit intense blue-violet, green, and red emissions upon ultraviolet excitation, with high photoluminescence quantum yields ranging from 54% to 93%. Furthermore, Cs3CeCl6, Cs3TbCl6, and Cs3EuCl6 metal halides exhibit intense radioluminescence spanning from the ultraviolet to the visible region. This research shows the potential of the scalable mechanochemical synthesis of lanthanide-based metal halides for the advancement of luminescent materials for scintillators.

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OBJECTIVES: This study aimed to establish clinically significant microRNA (miRNA) sets using extracellular vesicles (EVs) from bone marrow (BM) aspirates of patients with acute myelogenous leukemia (AML), and to identify the genes that interact with these EV-derived miRNAs in AML. MATERIALS AND METHODS: BM aspirates were collected from 32 patients with AML at the time of AML diagnosis. EVs were isolated using size-exclusion chromatography. A total of 965 EV-derived miRNAs were identified in all the samples. RESULTS: We analyzed the expression levels of these EV-derived miRNAs of the favorable (n = 10) and non-favorable (n = 22) risk groups; we identified 32 differentially expressed EV-derived miRNAs in the non-favorable risk group. The correlation of these miRNAs with risk stratification and patient survival was analyzed using the information of patients with AML from The Cancer Genome Atlas (TCGA) database. Of the miRNAs with downregulated expression in the non-favorable risk group, hsa-miR-181b and hsa-miR-143 were correlated with non-favorable risk and short overall survival. Regarding the miRNAs with upregulated expression in the non-favorable risk group, hsa-miR-188 and hsa-miR-501 were correlated with non-favorable risk and could predict poor survival. Through EV-derived miRNAs-mRNA network analysis using TCGA database, we identified 21 mRNAs that could be potential poor prognosis biomarkers. CONCLUSIONS: Overall, our findings revealed that EV-derived miRNAs can serve as biomarkers for risk stratification and prognosis in AML. In addition, these EV-derived miRNA-based bioinformatic analyses could help efficiently identify mRNAs with biomarker potential, similar to the previous cell-based approach.

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PURPOSE: Although rapid cognitive decline (RCD) is an important unfavorable prognostic factor, not much is known about it, especially in amyloid-negative individuals. The purpose of this study was to investigate risk factors for RCD in amyloid-negative individuals. PATIENTS AND METHODS: We retrospectively enrolled 741 individuals who were either cognitively unimpaired or had early-stage cognitive ability loss and who underwent 18F-florbetaben (FBB) (n = 402) or 18F-flutemetamol (FMM) (n = 339) PET/CT. Based on visual and semiquantitative (SUV ratio [SUVR]-based) analysis, the following amyloid-negative groups were established: visual-negative FBB (n = 232), visual-negative FMM (n = 161), SUVR-negative FBB (n = 104), and SUVR-negative FMM (n = 101). Univariable and multivariable logistic regression analyses were performed for RCD using 5 SUVRs, 5 cortical thicknesses, and 5 neuropsychological domains and clinico-demographic factors. RESULTS: In the amyloid-negative groups, a decline in language function was commonly identified as a significant risk factor for RCD (P = 0.0044 in the visual-negative FBB group, P = 0.0487 in the visual-negative FMM group, P = 0.0031 in the SUVR-negative FBB group, and P = 0.0030 in the SUVR-negative FMM group). In addition, declines in frontal/executive function, frontal SUVR, and parietal SUVR; a longer duration of education; and mild cognitive decline in the amyloid-negative groups were also significant risk factors for RCD. CONCLUSIONS: Even in amyloid-negative individuals without cognitive impairment or with early-stage cognitive ability loss, those with decreased language and frontal/executive functions on neuropsychological testing are at risk of progression to RCD.