Carbon materials and their metal composites for biomedical applications: A short review.

Carbon materials and their hybrid metal composites have garnered significant attention in biomedical applications due to their exceptional biocompatibility. This biocompatibility arises from their inherent chemical stability and low toxicity within biological systems. This review offers a comprehensive overview of carbon nanomaterials and their metal composites, emphasizing their biocompatibility-focused applications, including drug delivery, bioimaging, biosensing, and tissue engineering. The paper outlines advancements in surface modifications, coatings, and functionalization techniques designed to enhance the biocompatibility of carbon materials, ensuring minimal adverse effects in biological systems. A comprehensive investigation into hybrid composites integrating carbon nanomaterials is conducted, categorizing them as fullerenes, carbon quantum dots, carbon nanotubes, carbon nanofibers, graphene, and diamond-like carbon. The concluding section addresses regulatory considerations and challenges associated with integrating carbon materials into medical devices. This review culminates by providing insights into current achievements, challenges, and future directions, underscoring the pivotal role of carbon nanomaterials and their metal composites in advancing biocompatible applications.

Enhancing the cytotoxicity of immunotoxins by facilitating their dissociation from target receptors under the reducing conditions of the endocytic pathway.

Immunotoxins (ITs) are recombinant chimeric proteins that combine a protein toxin with a targeting moiety to facilitate the selective delivery of the toxin to cancer cells. Here, we present a novel strategy to enhance the cytosolic access of ITs by promoting their dissociation from target receptors under the reducing conditions of the endocytic pathway. We engineered monobodySS, a human fibronectin type III domain-based monobody with disulfide bond (SS)-containing paratopes, targeting receptors such as EGFR, EpCAM, Her2, and FAP. MonobodySS exhibited SS-dependent target receptor binding with a significant reduction in binding under reducing conditions. We then created monobodySS-based ITs carrying a 25 kDa fragment of Pseudomonas exotoxin A (PE25), termed monobodySS-PE25. These ITs showed dose-dependent cytotoxicity against target receptor-expressing cancer cells and a wider therapeutic window due to higher efficacy at lower doses compared to controls with SS reduction inhibited. ERSS/28-PE25, with a KD of 28 nM for EGFR, demonstrated superior tumor-killing potency compared to ER/21-PE25, which lacks an SS bond, at equivalent and lower doses. In vivo, ERSS/28-PE25 outperformed ER/21-PE25 in suppressing tumor growth in EGFR-overexpressing xenograft mouse models. This study presents a strategy for developing solid tumor-targeting ITs using SS-containing paratopes to enhance cytosolic delivery and antitumor efficacy.

Advancements in Asymmetric Supercapacitors: From Historical Milestones to Challenges and Future Directions.

Numerous challenges, like the uninterrupted supply of electricity, stable and reliable power, and energy storage during non-operational hours, arise across various industries due to the absence of advanced energy storage technologies. With the continual technological advancements in portable electronics, green energy, and transportation, there are inherent limitations in their innovative production. Thus, ongoing research is focused on pursuing sustainable energy storage technologies. An emerging solution lies in the development of asymmetric supercapacitors (ASCs), which offer the potential to extend their operational voltage limit beyond the thermodynamic breakdown voltage range of electrolytes. This is achieved by employing two distinct electrode materials, presenting an effective solution to the energy storage limitations faced by ASCs. The current review concentrates on the progression of working materials to develop authentic pseudocapacitive energy storage systems (ESS). Also, evaluates their ability to exceed energy storage constraints. It provides insights into fundamental energy storage mechanisms, performance evaluation methodologies, and recent advancements in electrode material strategies. The review approaches developing high-performance electrode materials and achieving efficient ASC types. It delves into critical aspects for enhancing the energy density of ASCs, presenting debates and prospects, thereby offering a comprehensive understanding and design principles for next-generation ASCs in diverse applications.

Strategy to Simultaneously Manipulate Direct Zn Nucleation and Hydrogen Evolution via Surface Modifier Hydrolysis for High-Performance Zn-Ion Batteries.

The demand for safer batteries is growing rapidly due to fire incidents in electronic devices that use Li-ion batteries. Zn-ion batteries are among the most promising candidates to replace Li-ion batteries because they use a water-based electrolyte and are not explosive. However, Zn-ion batteries suffer from persistent corrosion and dendritic crystal formation during the charge-discharge process, which decrease their reversibility and hinder their commercial usage. Extensive research has been conducted to address these issues, but there are significant limitations due to high process and time costs. In this study, the modulation of the Zn-electrolyte interface to overcome these challenges is attempted using acetamide-derived thioacetamide (TAA), a surface modifier used in electroplating. TAA undergoes hydrolysis in an aqueous solution and produces weakly acidic byproducts and sulfide ions. These species are adsorbed onto the Zn metal surface, which induces uniform Zn2+ deposition, facilitates the formation of a stable interfacial layer, and inhibits side reactions due to the reduced water activity. Consequently, the symmetric cell with TAA achieves a low polarization of 50 mV and stable cycling for 700 h at 1 mA cm-2. Additionally, a Zn|V6O13 full cell exhibits electrochemical reversibility, maintaining a capacity retention of 64% over 300 cycles. Therefore, this study offers useful insights into the development of a simple manufacturing process to ensure the competitiveness of Zn-ion batteries for practical applications using functional electrolyte additives.

Physical loads on upper extremity muscles while interacting with virtual objects in an augmented reality context.

Augmented reality (AR) environments are emerging as prominent user interfaces and gathering significant attention. However, the associated physical strain on the users presents a considerable challenge. Within this background, this study explores the impact of movement distance (MD) and target-to-user distance (TTU) on the physical load during drag-and-drop (DND) tasks in an AR environment. To address this objective, a user experiment was conducted utilizing a 5× 5 within-subject design with MD (16, 32, 48, 64, and 80 cm) and TTU (40, 80, 120, 160, and 200 cm) as the variables. Physical load was assessed using normalized electromyography (NEMG) (%MVC) indicators of the upper extremity muscles and the physical item of NASA-Task load index (TLX). The results revealed significant variations in the physical load based on MD and TTU. Specifically, both the NEMG and subjective physical workload values increased with increasing MD. Moreover, NEMG increased with decreasing TTU, whereas the subjective physical workload scores increased with increasing TTU. Interaction effects of MD and TTU on NEMG were also significantly observed. These findings suggest that considering the MD and TTU when developing content for interacting with AR objects in AR environments could potentially alleviate user load.

READRetro: natural product biosynthesis predicting with retrieval-augmented dual-view retrosynthesis.

Plants, as a sessile organism, produce various secondary metabolites to interact with the environment. These chemicals have fascinated the plant science community because of their ecological significance and notable biological activity. However, predicting the complete biosynthetic pathways from target molecules to metabolic building blocks remains a challenge. Here, we propose retrieval-augmented dual-view retrosynthesis (READRetro) as a practical bio-retrosynthesis tool to predict the biosynthetic pathways of plant natural products. Conventional bio-retrosynthesis models have been limited in their ability to predict biosynthetic pathways for natural products. READRetro was optimized for the prediction of complex metabolic pathways by incorporating cutting-edge deep learning architectures, an ensemble approach, and two retrievers. Evaluation of single- and multi-step retrosynthesis showed that each component of READRetro significantly improved its ability to predict biosynthetic pathways. READRetro was also able to propose the known pathways of secondary metabolites such as monoterpene indole alkaloids and the unknown pathway of menisdaurilide, demonstrating its applicability to real-world bio-retrosynthesis of plant natural products. For researchers interested in the biosynthesis and production of secondary metabolites, a user-friendly website (https://readretro.net) and the open-source code of READRetro have been made available.

The impact of CDCA5 expression on the immune microenvironment and its potential utility as a biomarker for PD-L1/PD-1 inhibitors in lung adenocarcinoma.

BACKGROUND: Studies have highlighted the important role of cell division cycle associated 5 (CDCA5) in tumor-associated immune dysfunction. We studied immune dysfunction based on CDCA5 expression in lung adenocarcinoma and investigated its potential as a biomarker for patients undergoing anti-programmed death protein-1/ programmed death ligand-1 (PD-1/PD-L1) inhibitor therapy. METHODS: We used the CIBERSORTx algorithm to investigate the immune cell distribution based on CDCA5 and explored its potential as a biomarker for PD-1/PD-L1 therapy using Tumor Immune Dysfunction and Exclusion in three lung adenocarcinoma datasets. Thus, we validated the role of CDCA5 as a biomarker in patients treated with PD-1/PD-L1 inhibitors. We also investigated the pathways through which CDCA5 regulates PD-L1 expression in a cell line. RESULTS: The high CDCA5 expression group showed elevated interferon gamma signature, CD274 expression, CD8+ T cell levels, tumor mutation burden, and microsatellite instability. Higher CDCA5 expression was associated with poorer prognosis in patients not treated with PD-1/PD-L1 inhibitors. However, in patients treated with PD-1/PD-L1 inhibitors, higher CDCA5 expression correlated with better response rates and prognosis. CDCA5 expression positively correlated with inhibitory immune checkpoint molecules. CDCA5 regulated the expression of PD-L1 through the ANXA/AKT pathway, and combined suppression of CDCA5 and PD-L1 synergistically inhibited cell proliferation. CONCLUSIONS: CDCA5 served as a promising biomarker for patients undergoing PD-L1/PD-1 inhibitor treatment, and co-inhibition of CDCA5 and PD-L1 could serve as an effective therapeutic strategy.

[Pediatric Hip Disorders]. / 소아 ê³ ê´€ì ˆ 질환.

Developmental dysplasia of the hip is a condition characterized by hip joint instability due to acetabular dysplasia in infancy, necessitating precise ultrasound examination. Legg-Calvé-Perthes disease is caused by a temporary disruption in blood flow to the femoral head during childhood, progressing through avascular, fragmentation, re-ossification, and residual stages. Slipped capital femoral epiphysis is a condition where the femoral head shifts medially along the epiphyseal line during adolescence due to stress, such as weight-bearing. Differentiating between transient hip synovitis and septic arthritis may require joint fluid aspiration. Osteomyelitis can be associated with soft tissue edema and osteolysis. When multiple lesions are present, it is essential to distinguish between Langerhans cell histiocytosis and metastatic neuroblastoma. This review will introduce imaging techniques and typical findings for these conditions.

Quantitative Bone SPECT/CT of Central Cartilaginous Bone Tumors: Relationship between SUVmax and Radiodensity in Hounsfield Unit.

(1) Background: it is challenging to determine the accurate grades of cartilaginous bone tumors. Using bone single photon emission computed tomography (SPECT)/computed tomography (CT), maximum standardized uptake value (SUVmax) was found to be significantly associated with different grades of cartilaginous bone tumor. The inquiry focused on the effect of the tumor matrix on SUVmax. (2) Methods: a total of 65 patients from 2017 to 2022 with central cartilaginous bone tumors, including enchondromas and low-to-intermediate grade chondrosarcomas, who had undergone bone SPECT/CT were retrospectively enrolled. The SUVmax was recorded and any aggressive CT findings of cartilaginous bone tumor and Hounsfield units (HU) of the chondroid matrix as mean, minimum, maximum, and standard deviation (SD) were reviewed on CT scans. Pearson's correlation analysis was performed to determine the relationship between CT features and SUVmax. Subgroup analysis was also performed between the benign group (enchondroma) and the malignant group (grade 1 and 2 chondrosarcoma) for comparison of HU values and SUVmax. (3) Results: a significant negative correlation between SUVmax and HU measurements, including HUmax, HUmean, and HUSD, was found. The subgroup analysis showed significantly higher SUVmax in the malignant group, with more frequent CT aggressive features, and significantly lower HUSD in the malignant group than in the benign group. (4) Conclusions: it was observed that higher SUVmax and lower HUSD were associated with a higher probability of having a low-to-intermediate chondrosarcoma with aggressive features and a less calcified tumor matrix.

Low-iodine-dose computed tomography coupled with an artificial intelligence-based contrast-boosting technique in children: a retrospective study on comparison with conventional-iodine-dose computed tomography.

BACKGROUND: Low-iodine-dose computed tomography (CT) protocols have emerged to mitigate the risks associated with contrast injection, often resulting in decreased image quality. OBJECTIVE: To evaluate the image quality of low-iodine-dose CT combined with an artificial intelligence (AI)-based contrast-boosting technique in abdominal CT, compared to a standard-iodine-dose protocol in children. MATERIALS AND METHODS: This single-center retrospective study included 35 pediatric patients (mean age 9.2 years, range 1-17 years) who underwent sequential abdominal CT scans-one with a standard-iodine-dose protocol (standard-dose group, Iobitridol 350 mgI/mL) and another with a low-iodine-dose protocol (low-dose group, Iohexol 240 mgI/mL)-within a 4-month interval from January 2022 to July 2022. The low-iodine CT protocol was reconstructed using an AI-based contrast-boosting technique (contrast-boosted group). Quantitative and qualitative parameters were measured in the three groups. For qualitative parameters, interobserver agreement was assessed using the intraclass correlation coefficient, and mean values were employed for subsequent analyses. For quantitative analysis of the three groups, repeated measures one-way analysis of variance with post hoc pairwise analysis was used. For qualitative analysis, the Friedman test followed by post hoc pairwise analysis was used. Paired t-tests were employed to compare radiation dose and iodine uptake between the standard- and low-dose groups. RESULTS: The standard-dose group exhibited higher attenuation, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) of organs and vessels compared to the low-dose group (all P-values < 0.05 except for liver SNR, P = 0.12). However, noise levels did not differ between the standard- and low-dose groups (P = 0.86). The contrast-boosted group had increased attenuation, CNR, and SNR of organs and vessels, and reduced noise compared with the low-dose group (all P < 0.05). The contrast-boosted group showed no differences in attenuation, CNR, and SNR of organs and vessels (all P > 0.05), and lower noise (P = 0.002), than the standard-dose group. In qualitative analysis, the contrast-boosted group did not differ regarding vessel enhancement and lesion conspicuity (P > 0.05) but had lower noise (P < 0.05) and higher organ enhancement and artifacts (all P < 0.05) than the standard-dose group. While iodine uptake was significantly reduced in low-iodine-dose CT (P < 0.001), there was no difference in radiation dose between standard- and low-iodine-dose CT (all P > 0.05). CONCLUSION: Low-iodine-dose abdominal CT, combined with an AI-based contrast-boosting technique exhibited comparable organ and vessel enhancement, as well as lesion conspicuity compared to standard-iodine-dose CT in children. Moreover, image noise decreased in the contrast-boosted group, albeit with an increase in artifacts.

Promotion of maturation of human pluripotent stem cell-derived cardiomyocytes via treatment with the peroxisome proliferator-activated receptor alpha agonist Fenofibrate.

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

Genetic tuning of intrinsically photosensitive retinal ganglion cell subtype identity to drive visual behavior.

The melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) comprise a subset of the ∼40 retinal ganglion cell types in the mouse retina and drive a diverse array of light-evoked behaviors from circadian photoentrainment to pupil constriction to contrast sensitivity for visual perception. Central to the ability of ipRGCs to control this diverse array of behaviors is the distinct complement of morphophysiological features and gene expression patterns found in the M1-M6 ipRGC subtypes. However, the genetic regulatory programs that give rise to subtypes of ipRGCs are unknown. Here, we identify the transcription factor Brn3b (Pou4f2) as a key genetic regulator that shapes the unique functions of ipRGC subtypes and their diverse downstream visual behaviors.

An ergonomic evaluation using a deep learning approach for assessing postural risks in a virtual reality-based smart manufacturing context.

This study proposes an integrated ergonomic evaluation designed to identify unsafe postures, whereby postural risks during industrial work are assessed in the context of virtual reality-based smart manufacturing. Unsafe postures were recognised by identifying the displacements of the centre of mass (COM) of body keypoints using a computer vision-based deep learning (DL) convolutional neural network approach. The risk levels for the identified unsafe postures were calculated using ergonomic risk assessment tools rapid upper limb assessment and rapid whole-body assessment. An analysis of variance was conducted to determine significant differences between the vertical and horizontal directions of postural movements associated with the most unsafe postures. The findings assess the ergonomic risk levels and identify the most unsafe postures during industrial work in smart manufacturing using DL method. The identified postural risks can help industry managers and researchers acquire a better understanding of unsafe postures.

This study aims to identify unsafe postures and calculate risk levels in a VR-based smart manufacturing context. Deep learning is applied to identify unsafe postures by detecting COM displacements and risk levels are calculated using ergonomic risk assessment tools. Results revealed the most unsafe body postures, crucial for workers' safety.

Diagnostic Pitfall and Clinical Characteristics of Variant Versus Wild-Type Transthyretin Amyloid Cardiomyopathy in Asian Population: The Korean Nationwide Cohort Study.

BACKGROUND: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an under-recognized cause of heart failure (HF) with clinical phenotypes that vary across regions and genotypes. We sought to characterize the clinical characteristics of ATTR-CM in Asia. METHODS: Data from a nationwide cohort of patients with ATTR-CM from six major tertiary centres in South Korea were analysed between 2010 and 2021. All patients underwent clinical evaluation, biochemical laboratory tests, echocardiography, and transthyretin (TTR) genotyping at the time of diagnosis. The study population comprised 105 Asian ATTR-CM patients (mean age: 69 years; male: 65.7%, wild-type ATTR-CM: 41.9%). RESULTS: Among our cohort, 18% of the patients had a mean left ventricular (LV) wall thickness < 12 mm. The diagnosis of ATTR-CM increased notably during the study period (8 [7.6%] during 2010-2013 vs. 22 [21.0%] during 2014-2017 vs. 75 [71.4%] during 2018-2021). Although the duration between symptom onset and diagnosis did not differ, the proportion of patients with HF presenting mild symptoms increased during the study period (25% NYHA class I/II between 2010-2013 to 77% between 2018-2021). In contrast to other international registry data, male predominance was less prominent in wild-type ATTR-CM (68.2%). The distribution of TTR variants was also different from Western countries and from Japan. Asp38Ala was the most common mutation. CONCLUSION: A nationwide cohort of ATTR-CM exhibited less male predominance, a proportion of patients without increased LV wall thickness, and distinct characteristics of genetic mutations, compared to cohorts in other parts of the world. Our results highlight the ethnic variation in ATTR-CM and may contribute to improving the screening process for ATTR-CM in the Asian population.

Association Between Objective Social Isolation and Unmet Medical Needs: A Nationwide Cross-sectional Study in Korea.

OBJECTIVES: The aim of this study was to analyze the relationship between objective social isolation (SI) and unmet medical needs (UMN) in adults aged 19 and older. METHODS: A cross-sectional analysis was conducted of 208 619 adults aged 19 and older, excluding missing data, using the 2019 Korea Community Health Survey. To analyze the association between objective SI and UMN, the chi-square test and logistic regression analysis were performed. RESULTS: The prevalence of UMN was 1.14 times higher (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.06 to 1.23) among those with SI than among those without SI, and the OR for groups with 5 SI types was 2.77 (95% CI, 1.86 to 4.12) compared to those with no SI types. In addition, a stratified analysis by age group showed that the association between SI and UMN existed even in groups under 64 years old. However, among those aged 65 and older, SI was associated with an OR of 1.53 (95% CI, 1.37 to 1.71) for UMN compared to non-SI. As the number of SI types increased, the prevalence of UMN also increased, indicating a strong association between SI and UMN in older adults. CONCLUSIONS: This study found that individuals with SI experienced UMN due to fear and anxiety about interpersonal relationships. Therefore, based on the results of this cross-sectional study, it is necessary to investigate the causal relationship between SI and UMN through future longitudinal data.

Shear wave elastography and dispersion imaging for hepatic veno-occlusive disease prediction after pediatric hematopoietic stem cell transplantation: a feasibility study.

BACKGROUND: Non-invasive imaging modalities are warranted for diagnosing and monitoring veno-occlusive disease because early diagnosis and treatment improve the prognosis. OBJECTIVE: To evaluate the usefulness of liver shear wave elastography (SWE) and shear wave dispersion (SWD) imaging in diagnosing and monitoring veno-occlusive disease in pediatric patients. MATERIALS AND METHODS: We conducted a prospective cohort study at a single tertiary hospital from March 2021 to April 2022. The study protocol included four ultrasound (US) sessions: a baseline US and three follow-up US after hematopoietic stem cell transplantation. Clinical criteria, including the European Society for Blood and Marrow Transplantation criteria, were used to diagnose veno-occlusive disease. We compared clinical factors and US parameters between the veno-occlusive disease and non-veno-occlusive disease groups. The diagnostic performance of US parameters for veno-occlusive disease was assessed by plotting receiver operating characteristic (ROC) curves. We describe temporal changes in US parameters before and after veno-occlusive disease diagnosis. RESULTS: Among the 38 participants (mean age 10.7 years), eight developed veno-occlusive disease occurring 17.0 ± 5.2 days after hematopoietic stem cell transplantation. Liver stiffness, as measured by SWE (15.0 ± 6.2 kPa vs. 5.8 ± 1.8 kPa; P<0.001), and viscosity, as assessed with SWD (17.7 ± 3.1 m/s/kHz vs. 14.3 ± 2.8 m/s/kHz; P=0.015), were significantly higher in the veno-occlusive disease group compared to the non-veno-occlusive disease group at the time of diagnosis. Liver stiffness demonstrated the highest area under the ROC (AUROC) curves at 0.960, with an optimal predictive value of >6.5 kPa, resulting in sensitivity and specificity of 100% and 83.3%, respectively. Viscosity demonstrated an AUROC of 0.783, with an optimal cutoff value of 13.9 m/s/kHz for predicting veno-occlusive disease, with a sensitivity of 100% and specificity of 53.3%, respectively. Liver stiffness increased with disease severity and decreased during post-treatment follow-up. CONCLUSION: SWE may be a promising technique for early diagnosis and severity prediction of veno-occlusive disease. Furthermore, liver viscosity assessed by SWD may serve as an additional marker of veno-occlusive disease.

Predictive value of plaque characteristics for identification of lesions causing ischemia.

BACKGROUND: Functional assessment using fractional flow reserve (FFR) and anatomical assessment using optical coherence tomography (OCT) are used in clinical practice for patients with intermediate coronary stenosis. Moreover, coronary computed tomography angiography (CTA) is a common noninvasive imaging technique for evaluating suspected coronary artery disease before being referred for angiography. This study aimed to investigate the association between FFR and plaque characteristics assessed using coronary CTA and OCT for intermediate coronary stenosis. METHODS: Based on a prospective multicenter registry, 159 patients having 339 coronary lesions with intermediate stenosis were included. All patients underwent coronary CTA before being referred for coronary angiography, and both FFR measurements and OCT examinations were performed during angiography. A stenotic lesion identified with FFR ≤0.80 was deemed diagnostic of an ischemia-causing lesion. The predictive value of plaque characteristics assessed using coronary CTA and OCT for identifying lesions causing ischemia was analyzed. RESULTS: Stenosis severity and plaque characteristics on coronary CTA and OCT differed between lesions that caused ischemia and those that did not. In multivariate analysis, low attenuation plaque on coronary CTA (odds ratio [OR]=2.78; P=0.038), thrombus (OR=5.13; P=0.042), plaque rupture (OR=3.25; P=0.017), and intimal vasculature on OCT (OR=2.57; P=0.012) were independent predictors of ischemic lesions. Increasing the number of these plaque characteristics offered incremental improvement in predicting the lesions causing ischemia. CONCLUSIONS: Comprehensive anatomical evaluation of coronary stenosis may provide additional supportive information for predicting the lesions causing ischemia.

Exploring aryl hydrocarbon receptor expression and distribution in the tumor microenvironment, with a focus on immune cells, in various solid cancer types.

Introduction: Aryl hydrocarbon receptor (AhR) is a transcription factor that performs various functions upon ligand activation. Several studies have explored the role of AhR expression in tumor progression and immune surveillance. Nevertheless, investigations on the distribution of AhR expression, specifically in cancer or immune cells in the tumor microenvironment (TME), remain limited. Examining the AhR expression and distribution in the TME is crucial for gaining insights into the mechanism of action of AhR-targeting anticancer agents and their potential as biomarkers. Methods: Here, we used multiplexed immunohistochemistry (mIHC) and image cytometry to investigate the AhR expression and distribution in 513 patient samples, of which 292 are patients with one of five solid cancer types. Additionally, we analyzed the nuclear and cytosolic distribution of AhR expression. Results: Our findings reveal that AhR expression was primarily localized in cancer cells, followed by stromal T cells and macrophages. Furthermore, we observed a positive correlation between the nuclear and cytosolic expression of AhR, indicating that the expression of AhR as a biomarker is independent of its localization. Interestingly, the expression patterns of AhR were categorized into three clusters based on the cancer type, with high AhR expression levels being found in regulatory T cells (Tregs) in non-small cell lung cancer (NSCLC). Discussion: These findings are anticipated to serve as pivotal evidence for the design of clinical trials and the analysis of the anticancer mechanisms of AhR-targeting therapies.