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Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined., Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months., Conclusion: This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as a key clinical tool over the past decade, but advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) and has two primary objectives: (1) assessing actionability for therapeutic options and (2) providing clarity for clinical questions. Of the 120 patients with various solid cancers who were enrolled, 95 (79%) successfully received genomic reports within a median of 11 working days from sampling to reporting. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability and 81% (13/16) pertaining to clinical clarity. These benefits include the selection of informed therapeutics and/or active clinical trials based on the identification of driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and suggests that it should be integrated into routine clinical practice to provide a complete image of the genomic landscape to enable tailored cancer management., (© 2024. The Author(s).)

While the molten salt-catalyzed chemical vapor deposition (CVD) technique is recognized for its effectiveness in producing large-area transition metal chalcogenides, understanding their growth mechanisms involving alkali metals remains a challenge. Here, we investigate the kinetics and mechanism of sodium-catalyzed molybdenum disulfide (MoS 2 ) growth and etching through image analysis conducted using an integrated CVD microscope. Sodium droplets, agglomerated via the thermal decomposition of the sodium cholate dispersant, catalyze the precipitation of supersaturated MoS 2 laminates and induce growth despite fragmentation during this process. Triangular MoS 2 crystals display a distinct self-exhausting exponential behavior and slow growth of thermodynamically favorable crystallographic faces, exhibiting a sulfur-dominant pressure. The growth and etching processes are facilitated by the scooting of sodium droplets along grain edges, displaying comparable rates. Leveraging these kinetics makes it possible to engineer atypical MoS 2 shapes. This combined microscope not only enhances the understanding of growth mechanisms but also contributes to the facile development of next-generation nanomaterials.

This research group (FROM) aimed to develop biomarkers for exposure to environmental hazards and diseases, assess environmental diseases, and apply and verify these biomarkers in environmentally vulnerable areas. Environmentally vulnerable areas—including refineries, abandoned metal mines, coal-fired power plants, waste incinerators, cement factories, and areas with high exposure to particulate matter—along with control areas, were selected for epidemiological investigations. A total of 1,157 adults, who had resided in these areas for over 10 years, were recruited between June 2021 and September 2023. Personal characteristics of the study participants were gathered through a survey. Biological samples, specifically blood and urine, were collected during the field investigations, separated under refrigerated conditions, and then transported to the laboratory for biomarker analysis. Analyses of heavy metals, environmental hazards, and adducts were conducted on these blood and urine samples. Additionally, omics analyses of epigenomes, proteomes, and metabolomes were performed using the blood samples. The biomarkers identified in this study will be utilized to assess the risk of environmental disease occurrence and to evaluate the impact on the health of residents in environmentally vulnerable areas, following the validation of diagnostic accuracy for these diseases.

Two-dimensional electrides can acquire topologically non-trivial phases due to intriguing interplay between the cationic atomic layers and anionic electron layers. However, experimental evidence of topological surface states has yet to be verified. Here, via angle-resolved photoemission spectroscopy (ARPES) and scanning tunnelling microscopy (STM), we probe the magnetic Weyl states of the ferromagnetic electride [Gd 2 C] 2+ ·2e - . In particular, the presence of Weyl cones and Fermi-arc states is demonstrated through photon energy-dependent ARPES measurements, agreeing with theoretical band structure calculations. Notably, the STM measurements reveal that the Fermi-arc states exist underneath a floating quantum electron liquid on the top Gd layer, forming double-stacked surface states in a heterostructure. Our work thus not only unveils the non-trivial topology of the [Gd 2 C] 2+ ·2e - electride but also realizes a surface heterostructure that can host phenomena distinct from the bulk., (© 2024. The Author(s).)

The pursuit of advanced brain-inspired electronic devices and memory technologies has led to explore novel materials by processing multimodal and multilevel tailored conductive properties as the next generation of semiconductor platforms, due to von Neumann architecture limits. Among such materials, antimony sulfide (Sb 2 S 3 ) thin films exhibit outstanding optical and electronic properties, and therefore, they are ideal for applications such as thin-film solar cells and nonvolatile memory systems. This study investigates the conduction modulation and memory functionalities of Sb 2 S 3 thin films deposited via the vapor transport deposition technique. Experimental results indicate that the Ag/Sb 2 S 3 /Pt device possesses properties suitable for memory applications, including low operational voltages, robust endurance, and reliable switching behavior. Further, the reproducibility and stability of these properties across different device batches validate the reliability of these devices for practical implementation. Moreover, Sb 2 S 3 -based memristors exhibit artificial neuroplasticity with prolonged stability, promising considerable advancements in neuromorphic computing. Leveraging the photosensitivity of Sb 2 S 3 enables the Ag/Sb 2 S 3 /Pt device to exhibit significant low operating potential and conductivity modulation under optical stimulation for memory applications. This research highlights the potential applications of Sb 2 S 3 in future memory devices and optoelectronics and in shaping electronics with versatility., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Current guidelines recommend complete revascularization (CR) in hemodynamically stable patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD). With regard to the timing of percutaneous coronary intervention (PCI) for non-infarct-related artery (non-IRA), recent randomized clinical trials have revealed that immediate CR was non-inferior to staged CR. However, the optimal timing of CR remains uncertain. The OPTION-STEMI trial compared immediate CR and in-hospital staged CR guided by fractional flow reserve (FFR) for intermediate stenosis of the non-IRA., Methods: The OPTION-STEMI is a multicenter, investigator-initiated, prospective, open-label, non-inferiority randomized clinical trial. The study included patients with at least 1 non-IRA lesion with ≥50% stenosis by visual estimation. Patients fulfilling the inclusion criteria were randomized into 2 groups at a 1:1 ratio: immediate CR (i.e., PCI for the non-IRA performed during primary angioplasty) or in-hospital staged CR. In the in-hospital staged CR group, PCI for non-IRA lesions was performed on another day during the index hospitalization. Non-IRA lesions with 50%-69% stenosis by visual estimation were evaluated by FFR, whereas those with ≥70% stenosis was revascularized without FFR. The primary endpoint was the composite of all-cause death, non-fatal myocardial infarction, and all unplanned revascularization at 1 year after randomization. Enrolment began in December 2019 and was completed in January 2024. The follow-up for the primary endpoint will be completed in January 2025, and primary results will be available in the middle of 2025., Conclusions: The OPTION-STEMI is a multicenter, non-inferiority, randomized trial that evaluated the timing of in-hospital CR with the aid of FFR in patients with STEMI and MVD., Trial Registration: URL: https://www., Clinicaltrials: gov. Unique identifier: NCT04626882; and URL: https://cris.nih.go.kr. Unique identifier: KCT0004457., Competing Interests: Conflicts of Interest The authors declare no disclosures or conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: To evaluate the effects of initiating sodium-glucose cotransporter-2 (SGLT2) inhibitors on cardiorenal outcomes and mortality compared to dipeptidyl peptidase-4 (DPP-4) inhibitors as active comparators in patients diagnosed with type 2 diabetes with a history of percutaneous coronary intervention (PCI)., Materials and Methods: We used an active-comparator, new-user design and nationwide data from the National Health Insurance Service in South Korea from 2014 to 2019. Of the 56 392 patients who underwent PCI, 4610 new SGLT2 inhibitor users were paired 1:1 with DPP-4 inhibitor users for analysis using propensity-score matching., Results: During 13 708.59 person-years of follow-up, the initiation of SGLT2 inhibitors, compared with the initiation of DPP-4 inhibitors, was associated with a significantly lower risk of composite repeat revascularization, myocardial infarction, stroke, heart failure (HF), all-cause death and end-stage renal disease (ESRD). The beneficial effects of SGLT2 inhibitor use were consistent with the components of stroke, HF, all-cause death and ESRD. In the cohort that included health examination data, including anthropometric and metabolic factors, new use of SGLT2 inhibitors was associated with a significantly lower risk of HF (hazard ratio [HR] 0.574, 95% confidence interval [CI] 0.36-0.915), all-cause death (HR 0.731, 95% CI 0.567-0.942), and ESRD (HR 0.076, 95% CI 0.018-0.319). The effects of SGLT2 inhibitor use were consistent regardless of the timing of the previous PCI., Conclusions: The initiation of SGLT2 inhibitors in patients with type 2 diabetes and a history of PCI was significantly associated with a reduced risk of cardiorenal consequences and mortality, irrespective of time since the last PCI., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

This cross-sectional study aimed to assess the interrelationships between PM 2.5 exposure, heavy metal concentrations, and oxidative stress indicators, while evaluating the impact of antioxidant intake, such as vitamins, on these associations. PM 2.5 exposure assessments were conducted using portable sensor-based monitors; biomarker analyses for heavy metals and oxidative stress were performed in 114 non-smoking adults. We observed that personal or ambient PM 2.5 exposure levels were not associated with increased levels of heavy metals in blood and urine, nor with oxidative stress levels in urine. However, the concentrations of cadmium and lead in blood, and those of chromium and nickel in urine, were significantly associated with the urinary malondialdehyde (MDA) concentration. Additionally, increases in blood cadmium, urinary chromium, and nickel levels were significantly associated with higher urinary MDA concentrations in the non-vitamin-supplement group, but this trend was not observed in the regular vitamin supplement group. Our findings suggest that a regular intake of vitamin supplements might modulate the relationship between heavy metal exposure and oxidative stress, indicating potential protective effects against oxidative damage induced by PM 2.5 and heavy metals. This study highlights the complexity of environmental pollutant exposure and its impact on human health, emphasizing the need for further research to elucidate the underlying mechanisms and explore potential protective strategies.

The novel coronavirus disease 2019 has stimulated the rapid development of new biological therapeutics to inhibit SARS-CoV-2 infection; however, this remains a challenging task. In a previous study using structural analysis, we revealed that human cyclophilin A inhibits the entry of SARS-CoV-2 into host cells by interfering with the interaction of the receptor-binding domain of the spike protein with angiotensin-converting enzyme 2 on the host cell surface, highlighting its potential for antiviral therapy. For a comprehensive experimental validation, in this study, we verified the antiviral effects of human cyclophilin A against SARS-CoV-2, including its variants, using in vitro assays and experiments on an in vivo mouse model. Human cyclophilin A demonstrated a highly effective antiviral effect, with an 85% survival rate upon SARS-CoV-2 infection. It also reduced viral titers, inflammation in the lungs and brain, and cytokine release in the serum, suggesting a controlled immune response and potentially faster recovery. Overall, our study provides insights into the potential of human cyclophilin A as a therapeutic agent against SARS-CoV-2, which should guide future clinical trials that might provide an additional therapeutic option for patients., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Aim: To investigate the efficacy and safety of pioglitazone compared to placebo when added to metformin plus dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, for patients with type 2 diabetes mellitus (T2DM)., Materials and Methods: In a multicentre study, with a randomized, double-blind, placebo-controlled design, 249 Korean patients with T2DM suboptimally managed on metformin and dapagliflozin were assigned to receive either pioglitazone (15 mg daily) or placebo for 24 weeks, followed by a 24-week pioglitazone extension. Primary outcomes included changes in glycated haemoglobin (HbA1c), with secondary outcomes assessing insulin resistance, adiponectin levels, lipid profiles, liver enzymes, body weight and waist circumference., Results: Pioglitazone administration resulted in a significant reduction in HbA1c levels (from 7.80% ± 0.72% to 7.27% ± 0.82%) compared with placebo (from 7.79% ± 0.76% to 7.69% ± 0.86%, corrected mean difference: -0.42% ± 0.08%; p < 0.01) at 24 weeks. Additional benefits from pioglitazone treatment included enhanced insulin sensitivity, increased adiponectin levels, raised high-density lipoprotein cholesterol levels and reduced liver enzyme levels, resulting in improvement in nonalcoholic fatty liver disease liver fat score. Despite no serious adverse events in either group, pioglitazone therapy was modestly but significantly associated with weight gain and increased waist circumference., Conclusions: Adjunctive pioglitazone treatment in T2DM inadequately controlled with metformin and dapagliflozin demonstrates considerable glycaemic improvement, metabolic benefits, and a low risk of hypoglycaemia. These advantages must be weighed against the potential for weight gain and increased waist circumference., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

This study focuses on advancing the field of remote sensing image target detection, addressing challenges such as small target detection, complex background handling, and dense target distribution. We propose solutions based on enhancing the YOLOv7 algorithm. Firstly, we improve the multi-scale feature enhancement (MFE) method of YOLOv7, enhancing its adaptability and precision in detecting small targets and complex backgrounds. Secondly, we design a modified YOLOv7 global information DP-MLP module to effectively capture and integrate global information, thereby improving target detection accuracy and robustness, especially in handling large-scale variations and complex scenes. Lastly, we explore a semi-supervised learning model (SSLM) target detection algorithm incorporating unlabeled data, leveraging information from unlabeled data to enhance the model's generalization ability and performance. Experimental results demonstrate that despite the outstanding performance of YOLOv7, the mean average precision (MAP) can still be improved by 1.9%. Specifically, under testing on the TGRS-HRRSD-Dataset, the MFE and DP-MLP models achieve MAP values of 93.4% and 93.1%, respectively. Across the NWPU VHR-10 dataset, the three models achieve MAP values of 93.1%, 92.1%, and 92.2%, respectively. Significant improvements are observed across various metrics compared to the original model. This study enhances the adaptability, accuracy, and generalization of remote sensing image object detection.

Meiosis is a highly complex process significantly influenced by transcriptional regulation. However, studies on the mechanisms that govern transcriptomic changes during meiosis, especially in prophase I, are limited. Here, we performed single-cell ATAC-seq of human testis tissues and observed reprogramming during the transition from zygotene to pachytene spermatocytes. This event, conserved in mice, involved the deactivation of genes associated with meiosis after reprogramming and the activation of those related to spermatogenesis before their functional onset. Furthermore, we identified 282 transcriptional regulators (TRs) that underwent activation or deactivation subsequent to this process. Evidence suggested that physical contact signals from Sertoli cells may regulate these TRs in spermatocytes, while secreted ENHO signals may alter metabolic patterns in these cells. Our results further indicated that defective transcriptional reprogramming may be associated with non-obstructive azoospermia (NOA). This study revealed the importance of both physical contact and secreted signals between Sertoli cells and germ cells in meiotic progression.

Innate immune training involves myelopoiesis, dynamic gene modulation, and functional reprogramming of myeloid cells in response to secondary heterologous challenges. The present study evaluates whether systemic innate immune training can protect tissues from local injury. Systemic pretreatment of mice with β-glucan, a trained immunity agonist, reduces the mortality rate of mice with bleomycin-induced lung injury and fibrosis, as well as decreasing collagen deposition in the lungs. β-Glucan pretreatment induces neutrophil accumulation in the lungs and enhances efferocytosis. Training of mice with β-glucan results in histone modification in both alveolar macrophages (AMs) and neighboring lung epithelial cells. Training also increases the production of RvD1 and soluble mediators by AMs and efferocytes. Efferocytosis increases trained immunity in AMs by stimulating RvD1 release, thus inducing SIRT1 expression in neighboring lung epithelial cells. Elevated epithelial SIRT1 expression is associated with decreased epithelial cell apoptosis after lung injury, attenuating tissue damage. Further, neutrophil depletion dampens the effects of β-glucan on macrophage accumulation, epigenetic modification in lung macrophages, epithelial SIRT1 expression, and injury-mediated fibrosis in the lung. These findings provide mechanistic insights into innate immune training and clues to the potential ability of centrally trained immunity to protect peripheral organs against injury-mediated disorders., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

In dye-sensitized solar cells (DSSCs), the counter electrode (CE) plays a crucial role as an electron transfer agent and regenerator of the redox couple. Unlike conventional CEs that are generally made of glass-based substrates (e.g., FTO/glass), polymer substrates appear to be emerging candidates, owing to their intrinsic properties of lightweight, high durability, and low cost. Despite great promise, current manufacturing methods of CEs on polymeric substrates suffer from serious limitations, including low conductivity, scalability, process complexity, and the need for dedicated vacuum equipment. In the present study, we employ and evaluate a fully additive manufacturing route that can enable the fabrication of CEs for DSSCs in a high-throughput and eco-friendly manner with improved performance. The proposed approach sequentially comprises: (1) material extrusion 3-D printing of polymer substrate; (2) conductive surface metallization through cold spray particle deposition; and (3) over-coating of a thin-layer catalyzer with a graphite pencil. The fabricated electrodes are characterized in terms of microstructure, electrical conductivity, and photo-conversion efficiency. Owing to its promising electrical conductivity (8.5 × 10 4 S·m -1 ) and micro-rough surface structure (R a ≈ 6.32 µm), the DSSCs with the additively manufactured CEs led to ≈2.5-times-higher photo-conversion efficiency than that of traditional CEs made of FTO/glass. The results of the study suggest that the proposed additive manufacturing approach can advance the field of DSSCs by addressing the limitations of conventional CE manufacturing platforms.

Background: Acute gastroenteritis (AGE) is a common cause of pediatric morbidity and mortality worldwide. AGE can cause an imbalance in the intestinal microbiota. This study aimed to investigate the diversity of the gut microbiome in Korean children hospitalized for infectious AGE at a university hospital., Methods: A total of 23 stool samples from patients aged 5 months to 11 years with AGE were analyzed. Thirteen convalescent stool samples were collected 1 month after discharge. Multiplex polymerase chain reaction (PCR) for the five viruses and 16 bacteria-specific AGE pathogens (PowerChek Multiplex Real time PCR Kit, Seoul, Korea), and 16s rRNA sequencing (Illumina MiSeq Sequencing system, Illumina, USA) were performed., Results: According to the results of multiplex PCR for causative pathogens, the microbiome taxonomic profile (MTP) of the gut microbiome in three groups of AGE, norovirus AGE (n = 11), Campylobacter AGE (n = 7) and Salmonella AGE (n = 5) was compared. The phylum Actinobacteria was significantly more abundant in the norovirus AGE (P = 0.011), whereas the phylum Proteobacteria was significantly more abundant in Salmonella AGE (P = 0.012). Alpha diversity, which indicates species richness and diversity, showed no statistical differences. However, beta diversity, representing the similarity in MTP between norovirus, Campylobacter, and Salmonella AGE, was significantly different (P = 0.007). In convalescence, compared with their corresponding AGE samples, the phylum Firmicutes; and the lower taxa Christensenellaceae (P = 0.0152) and Lachnospiraceae (P = 0.0327) were significantly increased., Conclusions: In pediatric AGE, the type of infectious agent can affect the diversity and dominance of gut microbiota in pediatric patients. Furthermore, healthy gut bacteria increased during the period of 1 month after infection, allowing a return to a healthy state without causing long-term dysbiosis., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background: Considering the interactions between heavy metals, a comprehensive evaluation of the effects of exposure to various types of co-interacting heavy metals on health is required. This study assessed the association between dyslipidemia markers and blood mercury, lead, cadmium, iron, zinc, and nickel levels in residents of an abandoned refinery plant., Methods: A total of 972 individuals (exposed group: 567, control group: 405) living near the Janghang refinery plant in the Republic of Korea were included. Blood mercury, lead, cadmium, iron, zinc, nickel, cholesterol, and triglyceride levels were measured. The combined effect of the six heavy metals on dyslipidemia markers was evaluated using a Bayesian kernel machine regression (BKMR) model and compared with the results of a linear regression analysis. The BKMR model results were compared using a stratified analysis of the exposed and control groups., Results: In the BKMR model, the combined effect of the six heavy metals was significantly associated with total cholesterol (TC) levels both below the 45th percentile and above the 55th percentile in the total population. The combined effect range between the 25th and 75th percentiles of the six metals on TC levels was larger in the exposed group than that in the total population. In the control group, the combined effects of the changes in concentration of the six heavy metals on the TC concentration were not statistically significant., Conclusion: These results suggest that the cholesterol levels of residents around the Janghang refinery plant may be elevated owing to exposure to multiple heavy metals., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

In this study, 1-bromohexyl-1methylpiperidinium bromide (Br-6-MPRD) ionic liquid grafted quaternized chitosan (QCS) and polyvinyl alcohol (PVA) blends were composited with glycidyl trimethyl ammonium chloride (GTMAC) quaternized silica (QSiO 2 ) at different dosages. Glutaraldehyde (GA) crosslinked the membranes and then processed into hydroxide form with an aqueous potassium hydroxide solution. The resultant IL-QCS/PVA/QSiO 2 membranes exhibit significantly improved ionic conductivity, moderate water absorption and swelling ratio compared with the pristine IL-QCS/PVA anion exchange membrane (AEM). Among them, the hydroxide ion conductivity and power density of IL-QCS/PVA/QSiO 2 -7 membrane can reach up to 78 mS cm -1 at 80 °C and 115 mW cm -2 at 60 °C respectively. In addition, IL-QCS/PVA/QSiO 2 membranes have excellent thermal, mechanical, and chemical stabilities, which can meet the application requirements of AEM for fuel cells., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Tumor cells of diffuse-type gastric cancer (DGC) are discohesive and infiltrate into the stroma as single cells or small subgroups, so the stroma significantly impacts DGC progression. Cancer-associated fibroblasts (CAFs) are major components of the tumor stroma. Here, we identified CAF-specific secreted molecules and investigated the mechanism underlying CAF-induced DGC progression., Methods: We conducted transcriptome analysis for paired normal fibroblast (NF)-CAF isolated from DGC patient tissues and proteomics for conditioned media (CM) of fibroblasts. The effects of fibroblasts on cancer cells were examined by transwell migration and soft agar assays, western blotting, and in vivo. We confirmed the effect of blocking tubulointerstitial nephritis antigen-like 1 (TINAGL1) in CAFs using siRNA or shRNA. We evaluated the expression of TINAGL1 protein in frozen tissues of DGC and paired normal stomach and mRNA in formalin-fixed, paraffin-embedded (FFPE) tissue using RNA in-situ hybridization (RNA-ISH)., Results: CAFs more highly expressed TINAGL1 than NFs. The co-culture of CAFs increased migration and tumorigenesis of DGC. Moreover, CAFs enhanced the phosphorylation of focal adhesion kinase (FAK) and mesenchymal marker expression in DGC cells. In an animal study, DGC tumors co-injected with CAFs showed aggressive phenotypes, including lymph node metastasis. However, increased phosphorylation of FAK and migration were reduced by blocking TINAGL1 in CAFs. In the tissues of DGC patients, TINAGL1 was higher in cancer than paired normal tissues and detected with collagen type I alpha 1 chain (COL1A1) in the same spot. Furthermore, high TINAGL1 expression was significantly correlated with poor prognosis in several public databases and our patient cohort diagnosed with DGC., Conclusions: These results indicate that TINAGL1 secreted by CAFs induces phosphorylation of FAK in DGC cells and promotes tumor progression. Thus, targeting TINAGL1 in CAFs can be a novel therapeutic strategy for DGC., (© 2024. The Author(s).)

Background: Distal radial access (DRA) as an alternative access route lacks evidence, despite its recent reputation., Objectives: The aim of this study was to evaluate the safety and feasibility of DRA on the basis of daily practice., Methods: The KODRA (Korean Prospective Registry for Evaluating the Safety and Efficacy of Distal Radial Approach) trial was a prospective multicenter registry conducted at 14 hospitals between September 2019 and September 2021. The primary endpoints were the success rates of coronary angiography (CAG) and percutaneous coronary intervention (PCI). The secondary endpoints included successful distal radial artery puncture, access-site crossover, access site-related complications, bleeding events, and predictors of puncture failure., Results: A total of 4,977 among 5,712 screened patients were recruited after the exclusion of 735 patients. The primary endpoints, the success rates of CAG and PCI via DRA, were 100% and 98.8%, respectively, among successful punctures of the distal radial artery (94.4%). Access-site crossover occurred in 333 patients (6.7%). The rates of distal radial artery occlusion and radial artery occlusion by palpation were 0.8% (36 of 4,340) and 0.8% (33 of 4,340) at 1-month follow-up. DRA-related bleeding events were observed in 3.3% of patients, without serious hematoma. Multilevel logistic regression analysis identified weak pulse (OR: 9.994; 95% CI: 7.252-13.774) and DRA experience <100 cases (OR: 2.187; 95% CI: 1.383-3.456) as predictors of puncture failure., Conclusions: In this large-scale prospective multicenter registry, DRA demonstrated high success rates of CAG and PCI, with a high rate of puncture success but low rates of distal radial artery occlusion, radial artery occlusion, bleeding events, and procedure-related complications. Weak pulse and DRA experience <100 cases were predictors of puncture failure. (Korean Prospective Registry for Evaluating the Safety and Efficacy of Distal Radial Approach [KODRA]; NCT04080700)., Competing Interests: Funding Support and Author Disclosures Samjin Pharmaceutical and the Gangwon Chapter of the Korean Society of Cardiology sponsored the KODRA trial. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Philodendron hederaceum (Jacq.) Schott 1829, a species of the Araceae family, is a foliage plant of ornamental value. The complete chloroplast genome sequence of Philodendron hederaceum was obtained by the de novo assembly of NovaSeq 6000 (Illumina Co., San Diego, CA) paired-end short reads and Oxford Nanopore long reads. The complete chloroplast genome of P. hederaceum was 168,609 bp in length, with a large single-copy (LSC) region of 94,393 bp, a small single-copy (SSC) region of 25,774 bp, and a pair of identical inverted repeat regions (IRs) of 24,221 bp. The genome contained a total of 129 genes, including 85 protein-coding genes, 36 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. The phylogenetic analysis of P. hederaceum with 19 related species and two outgroup species revealed the closest taxonomical relationship with Philodendron lanceolatum in the Araceae family., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

(1) Background: This study aimed to investigate the effects of proprioceptive neuromuscular facilitation pattern kinesio taping on arm swing, balance, and gait parameters among chronic stroke patients. (2) Methods: Twenty-eight participants were randomized into proprioceptive neuromuscular facilitation pattern kinesio taping during gait training ( n = 14) and gait training ( n = 14) groups. The proprioceptive neuromuscular facilitation pattern kinesio taping during gait training group employed proprioceptive neuromuscular facilitation pattern kinesio taping during 15 min treadmill-based gait training five times a week for four weeks, while the gait training group underwent the same gait training without proprioceptive neuromuscular facilitation pattern kinesio taping. Arm swing angle was measured using the Image J program, static balance was assessed with an AMTI force plate, dynamic balance was evaluated through the Timed Up and Go test, and gait parameters were recorded using the GAITRite system and the Dynamic Gait Index. (3) Results: After 4 weeks of training, the proprioceptive neuromuscular facilitation pattern kinesio taping during gait training group exhibited significant improvements in all variables compared to the baseline ( p < 0.05), whereas the gait training group did not show statistically significant differences in any variables ( p > 0.05). (4) Conclusions: This study demonstrates the effectiveness of proprioceptive neuromuscular facilitation pattern kinesio taping during gait training in enhancing arm swing angle, balance, and gait parameters., Competing Interests: The authors declare no conflicts of interest.

For centuries, natural products are regarded as vital medicines for human survival. Clematis terniflora var. mandshurica (Rupr.) Ohwi is an ingredient of the herbal medicine, Wei Ling Xian, which has been used in Chinese medicine to alleviate pain, fever, and inflammation. In particular, C. terniflora leaves have been used to cure various inflammatory diseases, including tonsillitis, cholelithiasis, and conjunctivitis. Based on these properties, this study aimed to scientifically investigate the anti-inflammatory effect of an ethanol extract of leaves of C. terniflora (EELCT) using activated macrophages that play central roles in inflammatory response. In this study, EELCT inhibited the essential inflammatory mediators, such as nitric oxide, cyclooxygenase-2, tumor necrosis factor- α , interleukin- (IL-) 6, IL-1 β , and inducible nitric oxide synthase, by suppressing the nuclear factor- κ B and mitogen-activated protein kinase activation in macrophages. Acute lung injury (ALI) is a fatal respiratory disease accompanied by serious inflammation. With high mortality rate, the disease has no effective treatments. Therefore, new therapeutic agents must be developed for ALI. We expected that EELCT can be a promising therapeutic agent for ALI by reducing inflammatory responses and evaluated its action in a lipopolysaccharide- (LPS-) induced ALI model. EELCT alleviated histological changes, immune cell infiltration, inflammatory mediator production, and protein-rich pulmonary edema during ALI. Collectively, our results may explain the traditional usage of C. terniflora in inflammatory diseases and suggest the promising potential of EELCT as therapeutic candidate for ALI., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Ji-Yeong Park et al.)

Purpose: We report a dosimetric study in whole breast irradiation (WBI) of plan robustness evaluation against position error with two radiation techniques: tangential intensity-modulated radiotherapy (T-IMRT) and multi-angle IMRT (M-IMRT)., Methods: Ten left-sided patients underwent WBI were selected. The dosimetric characteristics, biological evaluation and plan robustness were evaluated. The plan robustness quantification was performed by calculating the dose differences (Δ) of the original plan and perturbed plans, which were recalculated by introducing a 3-, 5-, and 10-mm shift in 18 directions., Results: M-IMRT showed better sparing of high-dose volume of organs at risk (OARs), but performed a larger low-dose irradiation volume of normal tissue. The greater shift worsened plan robustness. For a 10-mm perturbation, greater dose differences were observed in T-IMRT plans in nearly all directions, with higher Δ D 98% , Δ D 95% , and Δ D mean of CTV Boost and CTV. A 10-mm shift in inferior (I) direction induced CTV Boost in T-IMRT plans a 1.1 (Δ D 98% ), 1.1 (Δ D 95% ), and 1.7 (Δ D mean ) times dose differences greater than dose differences in M-IMRT plans. For CTV Boost, shifts in the right (R) and I directions generated greater dose differences in T-IMRT plans, while shifts in left (L) and superior (S) directions generated larger dose differences in M-IMRT plans. For CTV, T-IMRT plans showed higher sensitivity to a shift in the R direction. M-IMRT plans showed higher sensitivity to shifts in L, S, and I directions. For OARs, negligible dose differences were found in V 20 of the lungs and heart. Greater Δ D max of the left anterior descending artery (LAD) was seen in M-IMRT plans., Conclusion: We proposed a plan robustness evaluation method to determine the beam angle against position uncertainty accompanied by optimal dose distribution and OAR sparing., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: This study aimed to investigate the effects of repeated detection of non-alcoholic fatty liver disease (NAFLD) on the incidence risk of type 2 diabetes in young adults., Materials and Methods: In this nationwide population-based observational study using data from the Korean National Health Insurance Service, approximately 1 125 015 young adults aged 20-39 years who underwent health screening four times between 2009 and 2013 were included. NAFLD was defined as a fatty liver index (FLI) of ≥60. Repeated detection of NAFLD scores was defined as the number of times the participants met the criteria for NAFLD (0-4). To account for the degree of repeated detection of NAFLD, weighted repeated NAFLD scores were scaled as a sum by assigning points (0 points for FLI <30, 1 point for 30 ≤ FLI < 60, and 2 points for FLI ≥60) ranging from 0 to 8 points., Results: The multivariable-adjusted hazard ratios of type 2 diabetes associated with repeated detection of NAFLD scores of 1, 2, 3 and 4 were 2.74 (95% confidence interval 2.57-2.921), 3.45 (3.221-3.694), 4.588 (4.303-4.892) and 6.126 (5.77-6.504), respectively. The incidence risk of type 2 diabetes increased significantly with repeated detection of the NAFLD score. In the analysis of the weighted repeated NAFLD score, the hazard ratios for the incidence of type 2 diabetes showed a significant continuous positive linear association with increasing scores., Conclusions: Repeated detection of NAFLD influenced the incidence risk of type 2 diabetes in young adults, and a higher degree of repeated detection of NAFLD was independently associated with the risk of type 2 diabetes in young adults., (© 2023 John Wiley & Sons Ltd.)

Seasonal influenza results in 3 to 5 million cases of severe disease and 250,000 to 500,000 deaths annually. Macrophages have been implicated in both the resolution and progression of the disease, but the drivers of these outcomes are poorly understood. We probed mouse lung transcriptomic datasets using the Digital Cell Quantifier algorithm to predict immune cell subsets that correlated with mild or severe influenza A virus (IAV) infection outcomes. We identified a unique lung macrophage population that transcriptionally resembled small serosal cavity macrophages and whose presence correlated with mild disease. Until now, the study of serosal macrophage translocation in the context of viral infections has been neglected. Here, we show that pleural macrophages (PMs) migrate from the pleural cavity to the lung after infection with IAV. We found that the depletion of PMs increased morbidity and pulmonary inflammation. There were increased proinflammatory cytokines in the pleural cavity and an influx of neutrophils within the lung. Our results show that PMs are recruited to the lung during IAV infection and contribute to recovery from influenza. This study expands our knowledge of PM plasticity and identifies a source of lung macrophages independent of monocyte recruitment and local proliferation., Competing Interests: Competing interests statement:The authors declare no competing interest.

Objectives: To conduct a population-based analysis of the malignancy risks of patients with ankylosing spondylitis (AS)., Methods: A total of 1,796 patients with AS and 7,184 age- and sex-matched controls (1:4 ratio) were selected from the Korea National Health Insurance Service-National Sample Cohort database. Data of patients diagnosed with AS (code M45) according to the International Classification of Diseases (ICD) 10th edition, between 2002 and 2019, were reviewed. These data were extracted based on the ICD codes assigned to cancer patients., Results: Cancer developed in 168/1,796 patients (9.3%) after the AS diagnosis. After adjusting for confounders, the cancer risk of patients with AS was not significantly increased compared with that of controls (adjusted hazard ratio [HR]: 1.1; 95% confidence interval [CI]: 0.93-1.31). However, the risks for upper gastrointestinal (GI) cancer (adjusted HR: 1.51; 95% CI: 1.07-2.12) and haematologic malignancy (adjusted HR: 2.36; 95% CI: 1.2-4.65) were significantly higher in patients with AS than in controls. There were no significant differences in the risks for other major cancers between patients with AS and controls. Regarding medication for AS, the HR of upper GI cancer was higher in patients with AS compared with controls (adjusted HR: 1.51; 95% CI: 1.00-2.29)., Conclusion: The overall cancer risks in patients with AS were not significantly different compared with the controls. However, while the effect of non-steroidal anti-inflammatory drugs on upper GI cancer cannot be ruled out, patients with AS exhibited a significant increase in the risk of both upper GI cancer and hematologic malignancy., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To build a novel classifier using an optimized 3D-convolutional neural network for predicting high-grade small bowel obstruction (HGSBO)., Summary Background Data: Acute SBO is one of the most common acute abdominal diseases requiring urgent surgery. While artificial intelligence and abdominal computed tomography (CT) have been used to determine surgical treatment, differentiating normal cases, HGSBO requiring emergency surgery, and low-grade SBO (LGSBO) or paralytic ileus is difficult., Methods: A deep learning classifier was used to predict high-risk acute SBO patients using CT images at a tertiary hospital. Images from three groups of subjects (normal, nonsurgical, and surgical) were extracted; the dataset used in the study included 578 cases from 250 normal subjects, with 209 HGSBO and 119 LGSBO patients; over 38 000 CT images were used. Data were analyzed from 1 June 2022 to 5 February 2023. The classification performance was assessed based on accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve., Results: After fivefold cross-validation, the WideResNet classifier using dual-branch architecture with depth retention pooling achieved an accuracy of 72.6%, an area under receiver operating characteristic of 0.90, a sensitivity of 72.6%, a specificity of 86.3%, a positive predictive value of 74.1%, and a negative predictive value of 86.6% on all the test sets., Conclusions: These results show the satisfactory performance of the deep learning classifier in predicting HGSBO compared to the previous machine learning model. The novel 3D classifier with dual-branch architecture and depth retention pooling based on artificial intelligence algorithms could be a reliable screening and decision-support tool for high-risk patients with SBO., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Arsenic (As) is a human carcinogen widely distributed in the environment. This study evaluated the association between the urinary As concentration and single nucleotide polymorphisms (SNPs) in Korean adults to determine the genetic factors related to As concentration. The study included 496 participants for the genome-wide association study (GWAS) and 1483 participants for the candidate gene approach study. Participants were 19 years and older. The concentrations of total As (Tot As) and total As metabolites (Tmet As, the sum of inorganic As and their metabolites; arsenite, arsenate, monomethylarsonic, and dimethylarsinic acid) in the urine were analyzed. The GWAS identified four SNPs (rs1432523, rs3776006, rs11171747, and rs807573) associated with urinary Tot As and four SNPs (rs117605537, rs3776006, rs11171747, and rs148103384) significantly associated with urinary Tmet As concentration (P  < 1 × 10 -4 ). The candidate gene study identified two SNPs ( PRDX2 rs10427027 and GLRX rs3822751) in genes related to the reduction reaction associated with urinary Tot As and Tmet As. This study suggests that genetic factors may play a role in regulating As metabolism in the human body, affecting both exposure levels and its potential health risks in the general Korean population, even at low exposure levels., Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00216-x., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) under exclusive licence to Korean Society of Toxicology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Thromboembolic events (TEEs) are significant adverse events that can cause serious morbidities and mortality in cancer patients receiving chemotherapy. Patients with gastric cancer (GC) treated with palliative chemotherapy have been reported to experience a TEE incidence of 5-27%. However, very few reports have addressed TEEs in adjuvant chemotherapy (AC) for GC., Methods: This study retrospectively analyzed 611 GC patients (stage II: 309, III: 302) who started AC with capecitabine/oxaliplatin (167 patients) or S-1 (444 patients) after undergoing curative resection between January 2013 and June 2020 at a single center. The incidence of TEEs during AC or within 1 year after AC completion was investigated, while analyzing the factors that influenced the TEEs' occurrence., Results: TEEs were confirmed in 20 patients (3.3%), and TEEs occurred in almost all patients in the S-1 group (19 patients). The most common TEE types were cerebral infarction and pulmonary thromboembolism (five patients each). Although old age (≥ 70 years, p < 0.0001), S-1 treatment (p = 0.021), and hypertension (p = 0.017) were identified as significant risk factors for TEEs in univariate analysis, only old age showed a statistically significant correlation with TEEs' occurrence in multivariate analysis (odds ratio: 3.07; 95% confidence interval 1.11-8.48; p = 0.031)., Conclusions: TEEs occurred in fewer patients with GC who had been treated with AC than patients who had received palliative chemotherapy in previous reports. However, elderly GC patients who are undergoing AC require more careful surveillance for possible TEEs, considering relatively higher incidence of them., (© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Microglia are specialized brain-resident macrophages that arise from primitive macrophages colonizing the embryonic brain 1 . Microglia contribute to multiple aspects of brain development, but their precise roles in the early human brain remain poorly understood owing to limited access to relevant tissues 2-6 . The generation of brain organoids from human induced pluripotent stem cells recapitulates some key features of human embryonic brain development 7-10 . However, current approaches do not incorporate microglia or address their role in organoid maturation 11-21 . Here we generated microglia-sufficient brain organoids by coculturing brain organoids with primitive-like macrophages generated from the same human induced pluripotent stem cells (iMac) 22 . In organoid cocultures, iMac differentiated into cells with microglia-like phenotypes and functions (iMicro) and modulated neuronal progenitor cell (NPC) differentiation, limiting NPC proliferation and promoting axonogenesis. Mechanistically, iMicro contained high levels of PLIN2 + lipid droplets that exported cholesterol and its esters, which were taken up by NPCs in the organoids. We also detected PLIN2 + lipid droplet-loaded microglia in mouse and human embryonic brains. Overall, our approach substantially advances current human brain organoid approaches by incorporating microglial cells, as illustrated by the discovery of a key pathway of lipid-mediated crosstalk between microglia and NPCs that leads to improved neurogenesis., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Pulsed field ablation (PFA) is a nonthermal ablative strategy that achieves cell death via electroporation. Herein, we investigated the preclinical safety and efficacy of PFA using two novel 8-French, 16-electrode spiral PFA/mapping catheters (ElePulse; CRC EP, Inc.)., Methods: Bipolar PFA (>1.8 kV) was performed using 30 s, single-shot, QRS-gated applications. Altogether, 94 atrial structures were ablated in 23 swine, one canine, and one ovine, including right and left atria and atrial appendages, pulmonary veins, and superior and inferior (IVC) vena cavae. We also examined the impact of PFA on the phrenic nerve (14 swine) and on a deviated esophagus after delivery of PFA from inside the IVC (five swine)., Results: All applications were single-shot without catheter repositioning. Minimal microbubbling was observed without significant skeletal muscle twitching/activation (mean acceleration: 0.05 m/s 2 ). There was a marked reduction in post-PFA versus pre-PFA atrial electrogram amplitude (0.17 ± 0.21 vs. 1.18 ± 1.08 mV; p < .0001). Lesion durability was demonstrated up to 3 months in all targeted tissues. Histologically, lesions were contiguous and transmural, except in the atrial appendage, and without any thermal effects. Magnetic resonance, gross, and histologic examinations of the brain, rete mirabile, and kidneys revealed no thromboembolism. No acute/long-term phrenic nerve dysfunction was encountered. Although within 2 h of ablation, histologic examinations of the esophagus revealed acute PFA-related changes in the muscular layer, these completely resolved by 21 ± 5 days., Conclusion: A novel, single-shot, spiral PFA system is capable of safely creating large, durable atrial lesions without significant adverse effects on the phrenic nerve or the esophagus., (© 2023 Wiley Periodicals LLC.)

Genetically engineered mouse models (GEMMs) help us to understand human pathologies and develop new therapies, yet faithfully recapitulating human diseases in mice is challenging. Advances in genomics have highlighted the importance of non-coding regulatory genome sequences, which control spatiotemporal gene expression patterns and splicing in many human diseases 1,2 . Including regulatory extensive genomic regions, which requires large-scale genome engineering, should enhance the quality of disease modelling. Existing methods set limits on the size and efficiency of DNA delivery, hampering the routine creation of highly informative models that we call genomically rewritten and tailored GEMMs (GREAT-GEMMs). Here we describe 'mammalian switching antibiotic resistance markers progressively for integration' (mSwAP-In), a method for efficient genome rewriting in mouse embryonic stem cells. We demonstrate the use of mSwAP-In for iterative genome rewriting of up to 115 kb of a tailored Trp53 locus, as well as for humanization of mice using 116 kb and 180 kb human ACE2 loci. The ACE2 model recapitulated human ACE2 expression patterns and splicing, and notably, presented milder symptoms when challenged with SARS-CoV-2 compared with the existing K18-hACE2 model, thus representing a more human-like model of infection. Finally, we demonstrated serial genome writing by humanizing mouse Tmprss2 biallelically in the ACE2 GREAT-GEMM, highlighting the versatility of mSwAP-In in genome writing., (© 2023. The Author(s).)

Multistimuli responsive materials are advantageous in that they can enhance the desired response or bypass unwanted reactions. Light is one of the most attractive stimuli since it allows remote spatiotemporal control and multiplexing of properties (e.g., wavelength, intensity, irradiation time, pulsed/continuous wave) for application on multiphotoresponsive materials. However, the operating wavelength for such photoresponsive systems often includes an ultraviolet (UV) range that limits its use in the biomedical field. Herein, we investigate near-infrared (NIR)/visible (Vis) light-responsive nanocomposite films composed of rare earth element (i.e., Yb, Er)-doped NaYF 4 nanoparticles (NPs) embedded in azobenzene-incorporated poly(dimethylsiloxane) (AzoPDMS), silk fibroin, and silver nanowire (AgNW) layers. Photobending (PB) of the nanocomposite film is induced by a Vis light of 400-700 nm, while upconversion photoluminescence (UCPL) of embedded NPs is activated by an NIR light of 980 nm. The excitation wavelength of photoluminescence (PL) is shifted to the NIR (λ = 980 nm) range via photon upconversion in rare earth element-doped NPs. Independent operation of PB and UCPL enables both on-demand electrical switching and real-time location monitoring for spatiotemporally controlled electrical pulse stimulation. As a result, the dual-photoresponsive nanocomposite film can be utilized as a remotely controllable electrical stimulator and location indicator via different wavelengths of light.

Data regarding the clinical outcomes of older patients after Synergy everolimus-eluting stent (S-EES) implantation are limited. This study investigated the 12-month clinical outcomes of older patients who underwent percutaneous coronary intervention with new-generation drug-eluting stents according to ischemic risks. This prospective multicenter study targeted patients aged ≥75 years who underwent S-EES implantation. The primary and secondary end points included 12-month device-oriented composite end point (DOCE) (cardiovascular death, target vessel myocardial infarction, or target lesion revascularization) and major adverse cardiac and cerebrovascular events (MACCEs; all-cause death, myocardial infarction, target vessel revascularization, stent thrombosis, or stroke), respectively. A stratified analysis was conducted according to high-ischemic risk (HIR), defined as complex coronary intervention (number of stents implanted ≥3, total stented length >60 mm, chronic total occlusion, left main, or bifurcation), diabetes, or chronic kidney disease. In total, 650 enrolled patients aged ≥75 years were categorized into HIR (n = 425) and non-HIR groups (n = 225). In the total population, the 1-year incidence of DOCEs was 2.5%. The rates of DOCEs were not significantly different between the HIR and the non-HIR groups, whereas the MACCE rate was higher in the HIR (9.4%) than the non-HIR group (4.9%, p = 0.035), and the DOCE and MACCE components did not differ significantly in the occurrence between the groups. The independent predictors for the DOCEs or MACCEs included age, anemia, or left ventricular ejection fraction <40%. In conclusion, in older patients, S-EES implantation demonstrated favorable device-related outcomes, regardless of procedural complexity or co-morbidities. However, it requires careful attention because older patients with HIR are associated with worse clinical outcomes., Competing Interests: Declaration of Competing Interest Dr. B.K. Kim reports financial support was provided by Boston Scientific Corporation. The remaining authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Type 2 cytokines like IL-4 are hallmarks of helminth infection and activate macrophages to limit immunopathology and mediate helminth clearance. In addition to cytokines, nutrients and metabolites critically influence macrophage polarization. Choline is an essential nutrient known to support normal macrophage responses to lipopolysaccharide; however, its function in macrophages polarized by type 2 cytokines is unknown. Using murine IL-4-polarized macrophages, targeted lipidomics revealed significantly elevated levels of phosphatidylcholine, with select changes to other choline-containing lipid species. These changes were supported by the coordinated up-regulation of choline transport compared to naïve macrophages. Pharmacological inhibition of choline metabolism significantly suppressed several mitochondrial transcripts and dramatically inhibited select IL-4-responsive transcripts, most notably, Retnla. We further confirmed that blocking choline metabolism diminished IL-4-induced RELMα (encoded by Retnla) protein content and secretion and caused a dramatic reprogramming toward glycolytic metabolism. To better understand the physiological implications of these observations, naïve or mice infected with the intestinal helminth Heligmosomoides polygyrus were treated with the choline kinase α inhibitor, RSM-932A, to limit choline metabolism in vivo. Pharmacological inhibition of choline metabolism lowered RELMα expression across cell-types and tissues and led to the disappearance of peritoneal macrophages and B-1 lymphocytes and an influx of infiltrating monocytes. The impaired macrophage activation was associated with some loss in optimal immunity to H. polygyrus, with increased egg burden. Together, these data demonstrate that choline metabolism is required for macrophage RELMα induction, metabolic programming, and peritoneal immune homeostasis, which could have important implications in the context of other models of infection or cancer immunity., Competing Interests: The authors have declared that no conflict of interest exists., (Copyright: © 2023 Ghorbani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The purpose of this study was to confirm the antiproliferative and apoptotic induction potential of a saccharin and caffeine combination in ovarian cancer cells. The cell line used was Ovcar-3, and the cell viability was measured through a WST-8 assay, while a Chou-Talalay assay was used to confirm the synergistic effect of saccharin and caffeine on the ovarian cancer cells. A clonogenic assay, annexin V-FITC/PI-PE double-staining, and RT-PCR were performed to confirm the expression of genes that induce colony formation, cell viability, and apoptosis in ovarian cancer cells treated with the saccharin-caffeine combination. It was demonstrated that both saccharin and caffeine decreased the viability of Ovcar-3 cells, and the cell viability decreased even more significantly when the cells were treated with the combination of saccharin and caffeine. The clonogenic assay results showed that the number of colonies decreased the most when saccharin and caffeine were combined, and the number of colonies also significantly decreased compared to the single-treatment groups. Based on flow cytometry analysis using annexin V-FITC/PI-PE double-staining, it was confirmed that the decrease in cell viability caused by the combination of saccharin and caffeine was correlated with the induction of apoptosis. The results of the RT-PCR confirmed that the combined treatment of saccharin and caffeine promoted cell apoptosis by regulating the expression of apoptosis-inducing genes. These results demonstrate that the combination of saccharin and caffeine more efficiently inhibits the proliferation of Ovcar-3 cells and induces apoptosis in vitro.

Background: This study aimed to evaluate exposure to various hazardous substances emitted by incineration facilities and their likely effect on the health for residents of Bugi-myeon, Cheongju, Korea, which has three incineration facilities., Methods: Heavy metals, polycyclic aromatic hydrocarbons (PAHs), and dioxin concentrations in the air and soil of exposed and control areas were measured. Moreover, the exposure levels to harmful substances and its effects on health were investigated in 1,124 exposed and 232 control adults., Results: PAHs and dioxin concentrations in the air in the exposed area were significantly higher than in the control area. Urinary cadmium and PAHs metabolite concentrations were significantly higher in the exposed group than in the control group. The exposure group also had a higher prevalence of depression and self-reported allergic symptoms than the control group., Conclusion: The possibility of residents in Bugi-myeon being exposed to hazardous substances at incineration facilities cannot be ruled out. To prevent them from further exposure to hazardous substances, it is necessary to prohibit the expansion of additional incineration facilities in this area and to implement continuous monitoring projects for residents., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Recent emergence of low-dimensional unconventional superconductors and their exotic interface properties calls for new approaches to probe the pairing symmetry, a fundamental and frequently elusive property of the superconducting condensate. Here, we introduce the unique capability of tunneling Andreev reflection (TAR) to probe unconventional pairing symmetry, utilizing the sensitivity of this technique to specific Andreev reflections. Specifically, suppression of the lowest-order Andreev reflection due to quantum interference but emergence of the higher-order Andreev processes provides direct evidence of the sign-changing order parameter in the paradigmatic FeSe superconductor. TAR spectroscopy also reveals two superconducting gaps, points to a possibility of a nodal gap structure, and directly confirms that superconductivity is locally suppressed along the nematic twin boundary, with preferential and near-complete suppression of the larger energy gap. Our findings therefore enable new, atomic-scale insight into microscopic, inhomogeneous, and interfacial properties of emerging quantum materials.

Various prospective surgical trials have been conducted on treating patients with gastric cancer. In clinical practice, patients and surgeons may hesitate to participate in prospective surgical trials due to trial-related complications. In this study, we evaluated the effects of participation in prospective surgical trials on surgical outcomes after radical gastrectomy for gastric cancer. This study included 1689 patients who underwent curative gastrectomy for gastric cancer between 2016 and 2020. The propensity score weighting (PSW) method was used to adjust for differences in baseline clinicopathological characteristics between patients who participated and those who did not participate in prospective surgical clinical trials. Perioperative outcomes and overall survival were compared between groups. Of the 1689 patients, 309 (18.3%) participated in surgical clinical trials (SCT group). Before PSW, the SCT group had a similar operation time, intraoperative blood loss, complications, major complications, and hospital stay as the non-SCT group but had superior overall survival. After PSW, overall survival and perioperative outcomes were not significantly different between the groups. The present study suggests that participation in prospective surgical trials was not associated with surgical outcomes. Patients and surgeons may participate in prospective surgical trials without fearing adverse effects on surgical outcomes., (© 2023. Springer Nature Limited.)

Background/aims: The Genoss DES™ is a novel, biodegradable, polymer-coated, sirolimus-eluting stent with a cobalt- chromium stent platform and thin strut. Although the safety and effectiveness of this stent have been previously investigated, real-world clinical outcomes data are lacking. Therefore, the aim of this prospective, multicenter trial was to evaluate the clinical safety and effectiveness of the Genoss DES™ in all-comer patients undergoing percutaneous coronary intervention., Methods: The Genoss DES registry is a prospective, single-arm, observational trial for evaluation of clinical outcomes after Genoss DES™ implantation in all-comer patients undergoing percutaneous coronary intervention from 17 sites in South Korea. The primary endpoint was a device-oriented composite outcome of cardiac death, target vessel-related myocardial infarction (MI), and clinically driven target lesion revascularization (TLR) at 12 months., Results: A total of 1,999 patients (66.4 ± 11.1 years of age; 72.8% male) were analyzed. At baseline, 62.8% and 36.7% of patients had hypertension and diabetes, respectively. The implanted stent number, diameter, and length per patient were 1.5 ± 0.8, 3.1 ± 0.5 mm, and 37.0 ± 25.0 mm, respectively. The primary endpoint occurred in 1.8% patients, with a cardiac death rate of 1.1%, target vessel-related MI rate of 0.2%, and clinically driven TLR rate of 0.8%., Conclusion: In this real-world registry, the Genoss DES™ demonstrated excellent safety and effectiveness at 12 months among all-comer patients undergoing percutaneous coronary intervention. These findings suggest that the Genoss DES™ may be a viable treatment option for patients with coronary artery disease.

Background: Because spirometric parameters fail to address current status of asthma in some patients, additional tests are required for better evaluation of asthma., Objective: We aimed to test the ability of impulse oscillometry (IOS) and fractional expiratory nitric oxide (FeNO) in identifying inadequately controlled asthma (ICA) that was not uncovered by spirometry., Methods: Recruited asthmatic children between ages of 8 and 16 years underwent spirometry, IOS, and FeNO measurements on the same day. Only subjects who had spirometric indices within normal range were included. Asthma Control Questionnaire-6 scores of 0.75 or lower and greater than 0.75 indicated well-controlled asthma (WCA) and ICA. Percent predicted values of IOS parameters and IOS reference values for upper and lower limits of normal (>95th and <5th percentiles, respectively) were calculated on the basis of previously published equations., Results: There were no significant differences in all spirometric indices between the WCA (n = 59) and the ICA (n = 101) groups. The % predicted values of IOS parameters except resistance at 20 Hz (R20) were significantly different between the 2 groups. Receiver operating characteristic analysis showed that the highest and lowest areas under the curve were 0.81 and 0.67 for the difference between the resistances at 5 Hz and 20 Hz (R5-R20) and R20 in discrimination of ICA versus WCA. The areas under the curve for IOS parameters were improved by combination with FeNO. The better discriminative ability of IOS was also supported by the higher values of the concordance index for the resistance at 5 Hz (R5), R5-R20, the reactance at 5 Hz (X5), and the resonant frequency of reactance than those for spirometric parameters. Compared with those with normal values, subjects with abnormal IOS parameters or high FeNO had significantly higher odds of having ICA., Conclusions: The IOS parameters and FeNO were shown to be useful in identifying children with ICA when spirometry was normal., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Chennai, the capital city of Tamil Nadu in India, has experienced several instances of severe flooding over the past two decades, primarily attributed to persistent heavy rainfall. Accurate mapping of flood-prone regions in the basin is crucial for the comprehensive flood risk management. This study used the GIS-MCDA model, a multi-criteria decision analysis (MCDA) model that incorporated geographic information system (GIS) technology to support decision making processes. Remote sensing, GIS, and analytical hierarchy technique (AHP) were used to identify flood-prone zones and to determine the weights of various factors affecting flood risk, such as rainfall, distance to river, elevation, slope, land use/land cover, drainage density, soil type, and lithology. Four groups (zones) were identified by the flood susceptibility map including high, medium, low, and very low. These zones occupied 16.41%, 67.33%, 16.18%, and 0.08% of the area, respectively. Historical flood events in the study area coincided with the flood risk classification and flood vulnerability map. Regions situated close to rivers, characterized by low elevation, slope, and high runoff density were found to be more susceptible to flooding. The flood susceptibility map generated by the GIS-MCDA accurately described the flood-prone regions in the study area., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Heparins, naturally occurring glycosaminoglycans, are widely used for thrombosis prevention. Upon application as anticoagulants in cancer patients, heparins were found to possess additional antitumor activities. Ectonucleotidases have recently been proposed as novel targets for cancer immunotherapy., Methods and Results: In the present study, we discovered that heparin and its derivatives act as potent, selective, allosteric inhibitors of the poorly investigated ectonucleotidase NPP1 (nucleotide pyrophosphatase/phosphodiesterase-1, CD203a). Structure-activity relationships indicated that NPP1 inhibition could be separated from the compounds' antithrombotic effect. Moreover, unfractionated heparin (UFH) and different low molecular weight heparins (LMWHs) inhibited extracellular adenosine production by the NPP1-expressing glioma cell line U87 at therapeutically relevant concentrations. As a consequence, heparins inhibited the ability of U87 cell supernatants to induce CD4+ T cell differentiation into immunosuppressive Treg cells., Discussion: NPP1 inhibition likely contributes to the anti-cancer effects of heparins, and their specific optimization may lead to improved therapeutics for the immunotherapy of cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lopez, Schuh, Mirza, Vaaßen, Schmidt, Sylvester, Idris, Renn, Schäkel, Pelletier, Sévigny, Naggi, Scheffler, Lee, Bendas and Müller.)

Metal oxides (MOs) having Mg and Al with Mg/Al ratios of 1, 2, 3, and 4 were synthesized via calcination of the layered double hydroxides (LDH). The X-ray diffraction analysis revealed that all the MO consisted of periclase (MgO) crystallite with comparable crystallinity regardless of the metal ratio. According to the 27 Al magic-angle spinning nuclear magnetic resonance, the phase transformation from LDH to MO upon calcination facilitated the evolution of the Al 3+ ions with unsaturated coordination at the surface of MO. The specific surface area values of MOs were not significantly different from each other, ranging between 100 and 200 m 2 /g, suggesting that the metal ratio did not strongly influence the porous structure of MO. The temperature-dependent desorption of ammonia demonstrated that the Lewis acidity of the Al-rich MOs was the largest with an Mg/Al ratio of 1, attributed to the efficient exposure of the surface-active site Al 3+ -O 2- pairs. The acidity of heterogenous Al-rich MOs significantly increased with the exposed tetrahedral Al site on the surface and dramatically diminished when the molar ratio (Mg/Al) was over two.

Rice accounts for most of the calories consumed by the world's population. However, the whitebacked planthopper (WBPH), Sogatella furcifera (Horvath), is an insect that can cause rice yield loss. WBPH sucks the stems of rice and negatively affects yield and grain quality. Therefore, numerous insecticides have been developed to control WBPH in rice fields. However, chemical pesticides cause serious problems such as environmental pollution and ecosystem disturbance. Here, we research the possibility of using previously reported rice extracts obtained using methanol, Chrysoeriol 7(C7) and Cochlioquinone-9 (cq-9), as potential insect repellents. WBPH was caged with C7 or cq-9 and monitored, and the WBPH behavior was recorded. The number of WBPHs approaching the periphery of the C7 and cq-9 was very low. In cages containing the C7 and cq-9, only 13 and 7 WBPHs out of 100, respectively, walked around the material. In addition, foliar spraying with C7 and cq-9 did not negatively affect the plant height. The expression level of genes related to resistance was maintained at a high level in the resistant lines when treated with WBPHs alone, but was at a similar level to those of the controls when treated with C7 or cq-9. Interfering with WBPH access did not adversely affect the plant phenotype. Recently, people's interest in the environment has increased, and the use of plant-derived materials is also increasing. There is a new trend towards using plant extracts as an environmentally friendly means of managing resistance to WBPH during the rice cultivation period, while also avoiding environmental pollution.