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In-Sun Hong,1,2,* Gyu-Beom Jang,1,2,* Hwa-Yong Lee,3 Jeong-Seok Nam1,2 1Laboratory of Tumor Suppressor, Lee Gil Ya Cancer and Diabetes Institute, 2Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, 3The Faculty of Liberal Arts, Jungwon University, Chungbuk, Republic of Korea *These authors contributed equally to this work Abstract: Cancer stem cells (CSCs) have been shown to be markedly resistant to conventional cancer treatments such as chemotherapy and radiation therapy. Therefore, therapeutic strategies that selectively target CSCs will ultimately lead to better cancer treatments. Currently, accessible conventional therapeutic agents mainly eliminate the bulk tumor but do not eliminate CSCs. Therefore, the discovery and improvement of CSC-targeting therapeutic agents are necessary. Nanoparticles effectively inhibit multiple types of CSCs by targeting specific signaling pathways (Wnt/ß-catenin, Notch, transforming growth factor-ß, and hedgehog signaling) and/or specific markers (aldehyde dehydrogenases, CD44, CD90, and CD133) critically involved in CSC function and maintenance. In this review article, we summarized a number of findings to provide current information about their therapeutic potential of nanoparticles in various cancer cell types and CSCs. Keywords: ALDH, Wnt/ß-catenin, Hedgehog, Notch, TGF-ß signaling, CD44, CD133

Sangwha Lee,1,* Jongsung Kim,1,* Chung Wung Bark,2 Bonghee Lee,3 Heongkyu Ju,4 Se Chan Kang,5 TaeYoung Kim,6 Moon Il Kim,6 Young Tag Ko,3 Jeong-Seok Nam,3 Hyon Hee Yoon,1 Kyu-Sik Yun,1,6 Young Soo Yoon,1 Seong Soo A An,1,6 John Hulme6 1BioNano Sensor Research Center, 2Department of Electrical Engineering, Gachon University, Seongnam-si, 3Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 4Department of Nano-Physics, 5Department of Life Science, Gachon University, 6Department of BioNano Technology, Gachon BioNano Research Institute, Seongnam-si, South Korea *These authors contributed equally to this work Abstract: From the synergistic integration and the multidisciplinary strengths of the BioNano Sensor Research Center, Gachon Bionano Research Institute, and Lee GilYa Cancer and Diabetes Institute, researchers, students, and faculties at Gachon University in collaboration with other institutions in Korea, Australia, France, America, and Japan have come together to produce a special issue on the diverse applications of nano-theranostics in nanomedicine. This special issue will showcase new research conducted by various scientific groups in Gyonggi-do and Songdo/Incheon, South Korea. The objectives of this special issue are as follows: 1) to bring together and demonstrate some of the latest research results in the field, 2) to introduce new multifunctional nanomaterials and their applications in imaging and detection methods, and 3) to stimulate collaborative interdisciplinary research at both national and international levels in nanomedicine. Keywords: cancer, imaging and therapeutics, antibacterial, disease, neurodegenerative

The tribological properties of engineering and biological materials have been investigated at microscale levels through the calculation of the surface roughness and frictional coefficient using atomic force microscopy (AFM). Although a number of previous studies have reported the frictional coefficients of diverse bearing materials in total hip arthroplasty (THA), the relationship between the surface roughness and frictional coefficient of bearing materials of THA have not been reported, and furthermore, the tribological properties for different wear regions of a cobalt-chromium (Co-Cr) femoral head have not been well identified. Therefore, the objective of this study is to investigate the relationships between the surface roughness, frictional coefficient, and hardness for both the main-wear and the least-wear regions of a Co-Cr femoral head 10 years after THA. The average Vickers hardness of the Co-Cr femoral head was 380.7 +/- 11.3 HV. With the scanned area of 25 microm x 25 microm through AFM, the frictional coefficients of the main-wear and the least-wear regions were 0.229 +/- 0.054 and 0.243 +/- 0.059, respectively, and showed no statistical differences between these two regions (p = 0.449). However, differences in the surface roughness (Rq) between the main-wear region (Rq = 96.5 +/- 26.2 nm) and the least-wear region (Rq = 17.7 +/- 4.2 nm) were statistically significant (p < 0.0001). The results of the current study suggest that the frictional property of the Co-Cr femoral head is not significantly correlated with its surface roughness, and also provide guidelines for improving the surface characteristics of metallic implant materials. [ABSTRACT FROM AUTHOR]

We evaluated the role of oxidative stress in diabetic nephropathy by measuring intracellular reactive oxygen species (ROS) and redox-sensitive transcription factors in isolated peripheral mononuclear cells (PBMC) in 66 diabetic patients with or without diabetic nephropathy (Groups III and II, respectively) and 49 normal controls (Group I). Stimulated ROS was significantly higher in Group III compared to Group II (increment of H(2)O(2)-induced ROS production: 21.8+/-2.2% vs. 11.1+/-2.0%; increment of PMA-induced ROS production 23.5+/-4.5% vs. 21.6+/-2.2%; both respectively), and the activity of nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1), but not specificity protein 1 (Sp1) was significantly higher in Group III than in Group II (2.53-fold vs. 2.0-fold vs. 1.43-fold, respectively). Both PBMC- and urinary TGF-beta1 levels were higher in Group III than Group II (3.23+/-0.39 ng/g vs. 1.99+/-0.68 ng/g in PBMCs, 16.88+/-6.84 (ng/g Cr) vs. 5.61+/-1.57 (ng/g Cr) in urine, both respectively), and they correlated with the activity of NF-kappaB and AP-1 and 24-h urine albumin excretion (UAE). Increased intracellular ROS generation in PBMCs of diabetic patients is involved in the pathogenesis of diabetic nephropathy via activation NF-kappaB and AP-1 and an increased expression of TGF-beta1. [ABSTRACT FROM AUTHOR]

The cancer stem cell (CSC) hypothesis proposes that CSCs are the root of cancer and cause cancer metastasis and recurrence. In this study, we examined whether Ras signaling is associated with stemness of the CSCs population characterized by the stem cell antigen (Sca-1) phenotype in a 4T1 syngeneic mouse model of breast cancer. The Sca-1(pos) putative CSCs had high levels of activated Ras and phosphorylated MEK (p-MEK), compared with counterparts. The Ras farnesylation inhibitor (FTI-277) suppressed the maintenance and expansion of CSCs. Therefore, selective inhibition of Ras activation may be useful for stem-specific cancer therapy. [ABSTRACT FROM AUTHOR]

Carbon nanotubes (CNTs) produced by the floating-catalyst chemical vapor deposition (FCCVD) method are among the most promising nanomaterials of today, attracting interest from both academic and industrial sectors. These CNTs exhibit exceptional electrical conductivity, optical properties, and mechanical resilience due to their binder-free and low-defect structure, while the FCCVD method enables their continuous and scalable synthesis. Among the methodological FCCVD variations, aerosol CVD' is distinguished by its production of freestanding thin films comprising macroscale CNT networks, which exhibit superior performance and practical applicability. This review elucidates the complex interrelations between aerosol CVD reactor synthesis conditions and the resulting properties of the CNTs. A unified approach connecting all stages of the synthesis process is proposed as a comprehensive guide. This review examines the correlations between CNT structural parameters (length and diameter) and resultant film properties (conductivity, optical, and mechanical characteristics) to establish a comprehensive framework for optimizing CNT thin film synthesis. The analysis encompasses characterization methodologies specific to aerosol CVD-synthesized CNTs and evaluates how their properties influence applications across diverse domains, from energy devices to optoelectronics. The review concludes by addressing current challenges and prospects in this field., (© 2025 Wiley‐VCH GmbH.)

Autophagy is a crucial quality control mechanism that degrades damaged cellular components through lysosomal fusion with autophagosomes. However, elevated autophagy levels can promote drug resistance in cancer cells, enhancing their survival. Downregulation of autophagy through oxidative stress is a clinically promising strategy to counteract drug resistance, yet precise control of oxidative stress in autophagic proteins remains challenging. Here, a molecular design strategy of biocompatible neutral Ir(III) photosensitizers is demonstrated, B2 and B4, for precise reactive oxygen species (ROS) control at lysosomes to inhibit autophagy. The underlying molecular mechanisms for the biocompatibility and lysosome selectivity of Ir(III) complexes are explored by comparing B2 with the cationic or the non-lysosome-targeting analogs. Also, the biological mechanisms for autophagy inhibition via lysosomal oxidation are explored. Proteome analyses reveal significant oxidation of proteins essential for autophagy, including lysosomal and fusion-mediator proteins. These findings are verified in vitro, using mass spectrometry, live cell imaging, and a model SNARE complex. The anti-tumor efficacy of the precise lysosomal oxidation strategy is further validated in vivo with B4, engineered for red light absorbance. This study is expected to inspire the therapeutic use of spatiotemporal ROS control for sophisticated modulation of autophagy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objective: To determine the association between preoperative covert brain infarction following coronary angiography (CAG) and major adverse cardiac and cerebrovascular events (MACCEs) after coronary artery bypass grafting (CABG)., Design: A cohort study was conducted between January 2006 and December 2019, with the follow-up period concluding at either 5 years after surgery, the date of death, or April 27, 2023., Setting: A single tertiary center in Korea., Participants: Patients who underwent preoperative CAG and subsequent brain magnetic resonance imaging (MRI) before elective CABG., Interventions: None., Measurements and Main Results: The primary outcome was the incidence of MACCEs within 30 days of CABG. MACCEs included operative death (all-cause death within 30 days of surgery or before discharge), myocardial infarction, mechanical circulatory support, circulatory arrest, and stroke. Secondary outcomes included each component of MACCEs and all-cause mortality at 5 years after surgery. Of the 2,476 study patients (median [interquartile range] age: 65 [58-71] years; 24.7% were female), 212 (8.6%) had covert cerebral infarction on brain MRI after CAG but before CABG, and 353 (14.3%) patients experienced MACCEs after CABG. After performing 1:4 propensity-score matching, 1,057 patients were included in the final outcome analysis (212 with covert brain infarction and 845 without). The incidence of MACCEs within 30 days was not significantly different between patients with covert brain infarction and those without (15.1% [32/212] v 15.6% [132/845]; risk difference: -0.5, 95% confidence interval: -5.6 to 4.4; risk ratio: 0.97, 95% confidence interval: 0.66 to 1.32, p = 0.85). There were also no significant differences in each component of MACCEs within 30 days. There was no significant difference between the two groups regarding all-cause mortality at 5 years (18.7% v 17.0%, respectively, p for stratified log-rank test = 0.33)., Conclusions: Among patients undergoing elective CABG, there was no significant association between covert brain infarction following CAG and the occurrence of MACCEs within 30 days or long-term mortality after CABG., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The dynamic alteration of the tumor microenvironment (TME) serves as a driving force behind the progression and metastasis of colorectal cancer (CRC). Within the intricate TME, a pivotal player is the extracellular matrix (ECM), where modifications in components, degradation, and stiffness are considered critical factors in tumor development. In this study, we find that the membrane glycoprotein dysadherin directly targets matrix metalloprotease 9 (MMP9), initiating ECM remodeling within the TME and amplifying cancer progression. Mechanistically, the dysadherin/MMP9 axis not only enhances CRC cell invasiveness and ECM proteolytic activity but also activates cancer-associated fibroblasts, orchestrating the restructuring of the ECM through the synthesis of its components in human CRC cells, patient samples, and mouse models. Notably, disruption of ECM reorganization by dysadherin knockout results in a discernible reduction in the immunosuppressive and proangiogenic milieu in a humanized mouse model. Intriguingly, these effects are reversed upon the overexpression of MMP9, highlighting the intricate and pivotal role of the dysadherin/MMP9 axis in shaping the development of a malignant TME. Therefore, our findings not only highlight that dysadherin contributes to CRC progression by influencing the TME through ECM remodeling but also suggest that dysadherin may be a potential therapeutic target for CRC., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

This study presents an acetylene gas sensor capable of in situ monitoring transformer oils. This sensor utilizes carbon nanotubes (CNTs) embedded in polyimide (PI) synthesized by floating catalyst chemical vapor deposition. Unlike conventional sensors that target hydrocarbon gases dissolved in oil and measure the gas extracted from the oil, the proposed CNT-PI sensor detects gas within the oil in real time. The PI embedding technique effectively anchors and shields the CNT network against fluidic damage, ensuring stable sensing performance over 6 months, even under friction stress caused by oil convection. Decorating CNTs with gold nanoparticles further enhances the sensitivity and response of the sensor. The sensor achieves a high response (10.5% at 30 ppm) and fast response/recovery times (28 s/77 s), Furthermore, the sensor demonstrates good response (10.4% at 30 ppm) and moderate response/recovery times (444 s/670 s) in an oil medium, which qualifies for industrial applications. Additionally, a CNT-PI-based heater is integrated into the sensor as a multilayer component, maintaining an optimal operating temperature of 90 °C. The CNT-PI sensor demonstrates consistent gas-sensing performance even after 10,000 bending cycles and exhibits superior characteristics, indicating its compatibility with various forms of transformers., (© 2024 Wiley‐VCH GmbH.)

The role of biomarkers in cancer treatment varies significantly depending on the cancer stage. Thus, in clinical practice, tailoring biomarkers to meet the specific needs and challenges of each cancer stage can increase the precision of treatment. Because they reflect underlying genetic alterations that influence cancer progression, copy number variation (CNV) biomarkers can play crucial prognostic roles. In our previous study, we identified potential survival-related genes for colorectal cancer (CRC) by analyzing CNV and gene expression data using a machine-learning approach. To further investigate the biological function of NRXN1, we assessed the use of RNA sequencing, phosphokinase assays, real-time quantitative PCR, and Western blot analysis. We found that NRXN1 copy number deletion was significantly associated with poor overall survival (OS) and recurrence-free survival (RFS), even in patients who received adjuvant chemotherapy. Compared with its expression in normal tissues, NRXN1 expression was lower in tumors, suggesting its potential role as a tumor suppressor. NRXN1 knockdown enhanced CRC cell viability and invasion, and transcriptome analysis indicated that the increased invasion was caused by GSK3β-mediated epithelial-mesenchymal transition. These findings highlight NRXN1 copy number deletion as a novel biomarker for predicting recurrence and survival in patients with resected colon cancer.

Hydrogen sulfide (H 2 S) can regulate biological processes by post-translational persulfidation of proteins at select cysteine residues. In this issue of Molecular Cell, Zheng et al. 1 identify the enzyme SAHH as an H 2 S substrate, which upon persulfidation disrupts homocysteine metabolism and sensitizes lung cancer cells to ferroptosis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The IL-23-Th17 axis is responsible for neutrophilic inflammation in various inflammatory diseases. Here, we discover a potential pathway to inhibit neutrophilic asthma. In our neutrophil-dominant asthma (NDA) model, single-cell RNA-seq analysis identifies a subpopulation of CD39 + CD9 + interstitial macrophages (IMs) suppressed by IL-23 in NDA conditions but increased by an IL-23 inhibitor αIL-23p19. Adoptively transferred CD39 + CD9 + IMs suppress neutrophil extracellular trap formation (NETosis), a representative phenotype of NDA, and also Th17 cell activation and neutrophilic inflammation. CD39 + CD9 + IMs first attach to neutrophils in a CD9-dependent manner, and then remove ATP near neutrophils that contribute to NETosis in a CD39-dependent manner. Transcriptomic data from asthmatic patients finally show decreased CD39 + CD9 + IMs in severe asthma than mild/moderate asthma. Our results suggest that CD39 + CD9 + IMs function as a potent negative regulator of neutrophilic inflammation by suppressing NETosis in the IL-23-Th17 axis and can thus serve as a potential therapeutic target for IL-23-Th17-mediated neutrophilic asthma., (© 2024. The Author(s).)

Background: Remimazolam is a recently marketed ultrashort-acting benzodiazepine. This drug is considered safe and effective during general anesthesia; however, limited information is available about its effects on patients undergoing cardiac surgery. Therefore, the present study was conducted to evaluate the efficacy and hemodynamic stability of a bolus administration of remimazolam during anesthesia induction in patients undergoing cardiac surgery., Methods: Patients undergoing elective cardiac surgery were randomly assigned to any 1 of the following 3 groups: anesthesia induction with a continuous infusion of remimazolam 6 mg/kg/h (continuous group), a single-bolus injection of remimazolam 0.1 mg/kg (bolus 0.1 group), or a single-bolus injection of remimazolam 0.2 mg/kg (bolus 0.2 group). Time to loss of responsiveness, defined as modified Observer's Assessment of Alertness/Sedation Scale <3, and changes in hemodynamic status during anesthetic induction were measured., Results: Times to loss of responsiveness were 137 ± 20, 71 ± 35, and 48 ± 9 seconds in the continuous, bolus 0.1, and bolus 0.2 groups, respectively. The greatest mean difference was observed between the continuous and bolus 0.2 groups (89.0, 95% confidence interval [CI], 79.1-98.9), followed by the continuous and bolus 0.1 groups (65.8, 95% CI, 46.9-84.7), and lastly between the bolus 0.2 and bolus 0.1 groups (23.2, 95% CI, 6.6-39.8). No significant differences were found in terms of arterial blood pressures and heart rates of the patients., Conclusions: A single-bolus injection of remimazolam provided efficient anesthetic induction in patients undergoing cardiac surgery. A 0.2 mg/kg bolus injection of remimazolam resulted in the shortest time to loss of responsiveness among the 3 groups, without significantly altering the hemodynamic parameters. Therefore, this dosing can be considered a favorable anesthetic induction method for patients undergoing cardiac surgery., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Background: Minimalist transcatheter aortic valve replacement (TAVR) under monitored anesthesia care (MAC) emphasizes early recovery. Remimazolam is a novel benzodiazepine with a short recovery time. This study hypothesized that remimazolam is non-inferior to dexmedetomidine in terms of recovery after TAVR., Methods: In this retrospective observational study, remimazolam was compared to dexmedetomidine in patients who underwent TAVR under MAC at a tertiary academic hospital between July 2020 and July 2022. The primary outcome was timely recovery after TAVR, defined as discharge from the intensive care unit within the first day following the procedure. Propensity score matching was used to compare timely recovery between remimazolam and dexmedetomidine, applying a non-inferiority margin of -10%., Results: The study included 464 patients, of whom 218 received remimazolam and 246 received dexmedetomidine. After propensity score matching, 164 patients in each group were included in the analysis. Regarding timely recovery after TAVR, remimazolam was non-inferior to dexmedetomidine (152 of 164 [92.7%] in the remimazolam group versus 153 of 164 [93.3%] in the dexmedetomidine group, risk difference [95% CI]: -0.6% [-6.7%, 5.5%]). The use of remimazolam was associated with fewer postoperative vasopressors/inotropes (21 of 164 [12.8%] vs. 39 of 164 [23.8%]) and temporary pacemakers (TPMs) (76 of 164 [46.3%] vs. 108 of 164 [65.9%]) compared to dexmedetomidine., Conclusions: In patients undergoing TAVR under MAC, remimazolam was non-inferior to dexmedetomidine in terms of timely recovery. Remimazolam may be associated with better postoperative recovery profiles, including a lesser need for vasopressors/inotropes and TPMs.

Background/objectives: The tumor microenvironment (TME) has emerged as a significant prognostic factor. This study aimed to identify prognostic factors by combining clinicopathologic parameters and the TME biomarkers in patients who underwent surgery following neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC)., Methods: CD8 + T cells, CXCR3, CXCL10, and α-smooth muscle actin (α-SMA) were analyzed via immunohistochemical staining. We also incorporated AI-powered digital pathology to assess the spatial TME. The associations between these biomarkers, clinicopathologic parameters, and survival outcomes were evaluated., Results: CD8 + T cell expression, CXCR3 expression in tumor-infiltrating lymphocytes (TILs), and immune phenotypes were correlated. LARC patients with a high expression of CD8 + T cells, CXCR3 in TILs, and an inflamed phenotype had a significantly better prognosis than their counterparts did. In the multivariate analysis, the expression of CD8 + T cells and the inflamed/immune-excluded phenotype were significant tumor immune microenvironment (TiME) biomarkers for recurrence-free survival (RFS) but not for overall survival (OS). Notably, patients with the immune-desert phenotype had a poor prognosis regardless of pathologic stage, even if postoperative chemotherapy was administered ( p < 0.001)., Conclusions: CD8 + T cells and AI-powered immune phenotypes, alongside clinical factors, can guide personalized treatment in LARC patients receiving nCRT. A therapeutic strategy to modify the TiME after nCRT could help reduce recurrence after surgery.

Background: Tranexamic acid (TXA) effectively attenuates hyperfibrinolysis and preemptive administration has been employed to reduce bleeding and blood transfusions in various surgical settings. However, TXA administration could be associated with adverse effects, such as seizures and thromboembolic risks. While patients with fibrinolysis shutdown showed greater thromboembolic complications and mortality, TXA administration may aggravate the degree of shutdown in these patients. Selective TXA administration based on the results of rotational thromboelastometry (ROTEM) would be non-inferior to preemptive TXA administration in reducing postoperative bleeding and beneficial in reducing its risks in patients undergoing cardiovascular surgery., Methods: This non-inferiority, randomized, double-blind, placebo-controlled, multicenter trial will be performed in 3 tertiary university hospitals from August 2023 to March 2025. Seven hundred sixty-four patients undergoing cardiovascular surgery will be randomly allocated to get TXA as a preemptive (Group-P) or goal-directed strategy (Group-GDT) in each institution (with a 1:1 allocation ratio). After anesthesia induction, TXA (10 mg/kg and 2 mg/kg/h) and a placebo are administered after anesthesia induction in Group-P and Group-GDT, respectively. ROTEM tests are performed immediately before weaning from CPB and at the considerable bleeding post-CPB period. After getting the test results, a placebo is administered in Group-P (regardless of the test results). In Group-GDT, placebo or TXA is administered according to the results: placebo is administered if the amplitude at 10 min (A10-EXTEM) is ≥ 40 mm and lysis within 60 min (LI60-EXTEM) of EXTEM assay is ≥ 85%, or TXA (20 mg/kg) is administered if A10-EXTEM is < 40 mm or LI60-EXTEM is < 85%. The primary outcome is inter-group comparisons of postoperative bleeding (for 24 h). The secondary measures include comparisons of perioperative blood transfusion, coagulation profiles, reoperation, thromboembolic complications, seizures, in-hospital mortality, fibrinolysis phenotypes, and hospital costs., Discussion: The absence of inter-group differences in postoperative bleeding would support the selective strategy's non-inferiority in reducing postoperative bleeding in these patients. The possible reduction in thromboembolic risks, seizures, and fibrinolysis shutdown in Group-GDT would support its superiority in reducing TXA-induced adverse events and the cost of their management., Trial Registration: This trial was registered at ClinicalTrials.gov with the registration number NCT05806346 on March 28, 2023., Trial Status: recruiting. Issue date: 2023 March 28 (by Tae-Yop Kim, MD, PhD). The trial was registered in the clinical registration on March 28, 2023 (ClinicalTrials.gov, NCT05806346) and revised to the latest version of its protocol (version no. 8, August 26, 2024) approved by the institutional review boards (IRBs) of all 3 university hospitals (Konkuk University Medical Center, 2023-07-005-001, Asan Medical Center, 2023-0248, and Samsung Medical Center, SMC 2023-06-048-002). Its recruitment was started on August 1, 2023, and will be completed on December 31, 2024. Protocol amendment number: 08 (protocol version 08, August 26, 2024). Revision chronology: 2023 March 28:Original. 2023 April 10:Amendment No 01. The primary reason for the amendment is the modification of Arms (adding one arm for sub-group analyses) and Interventions, Outcome Measures, Study Design, Study Description, Study Status, Eligibility, and Study Identification. 2023 May 03:Amendment No 02. The primary reason for the amendment is to modify the Outcome Measures and update the study status. 2023 July 06:Amendment No 03. The primary reason for amendment is to update the chronological study status. 2023 July 07:Amendment No 04. The primary reason for the amendment is the modification of study information (the treatment category was changed to diagnostic, and Phase 4 was changed to not applicable) and a chronological update on the study status. 2023 September 12:Amendment No 06. The primary reason for the amendment is a chronological update in the study status and the inclusion of additional information regarding contacts/locations and oversight. 2023 December 29:Amendment No 07. The primary reason for the amendment is to modify the outcome measures (including detailed information on outcome measures, addition of extra secondary measures, and chronological updates in study status). 2024 August 26:Amendment No 08. The primary reason for the amendment is to add detailed descriptions regarding data handling and the names and roles of the participating institutions and to update the chronological process of the trial., (© 2024. The Author(s).)

Objectives: To determine whether balanced solutions can reduce the incidence of acute kidney injury after off-pump coronary artery bypass surgery compared with saline., Design: Randomized controlled trial., Setting: Single tertiary care center., Participants: Patients who underwent off-pump coronary artery bypass surgery between June 2014 and July 2020., Interventions: Balanced solution-based chloride-restrictive intravenous fluid strategy., Measurements and Main Results: The primary outcome was acute kidney injury within 7 postoperative days, as defined by the 2012 Kidney Disease: Improving Global Outcomes Clinical Practice Guideline. The incidence of acute kidney injury was 4.4% (8/180) in the balanced group and 7.3% (13/178) in the saline group. The difference was not statistically significant (risk difference, -2.86%; 95% confidence interval [CI], -7.72% to 2.01%; risk ratio, 0.61, 95% CI, 0.26 to 1.43; p = 0.35). Compared with the balanced group, the saline group had higher levels of intraoperative serum chloride and lower base excess, which resulted in a lower pH., Conclusions: In patients undergoing off-pump bypass surgery with a normal estimated glomerular filtration rate, the intraoperative balanced solution-based chloride-restrictive intravenous fluid administration strategy did not decrease the rate of postoperative acute kidney injury compared with the saline-based chloride-liberal intravenous fluid administration strategy., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Previous studies have demonstrated conflicting results regarding the effects of rehabilitation therapy on poststroke mortality. We aimed to investigate the association between rehabilitation therapy, including both inpatient and outpatient treatment, within the first 6 months after stroke and long-term all-cause mortality in patients with stroke using the Korean National Health Insurance System data., Methods: A total of 10 974 patients newly diagnosed with stroke using the International Classification of Diseases , Tenth Revision , codes (I60-I64) between 2003 and 2019 were enrolled and followed up for all-cause mortality until 2019. Follow-up for mortality began 6 months after the index event. Poststroke patients were categorized into 3 groups according to the frequency of rehabilitation therapy: no rehabilitation therapy, ≤40 sessions and >40 sessions. Cox proportional hazards models were used to assess the mortality risk according to rehabilitation therapy stratified by disability severity measured based on activities of daily living 6 months after stroke onset., Results: Within 6 months after stroke, 6738 patients (61.4%) did not receive rehabilitation therapy, whereas 2122 (19.3%) received ≤40 sessions and 2114 (19.3%) received >40 sessions of rehabilitation therapy. Higher frequency of rehabilitation therapy was associated with significantly lower poststroke mortality in comparison to no rehabilitation therapy (hazard ratio [HR], 0.88 [95% CI, 0.79-0.99]), especially among individuals with severe disability after stroke (mild to moderate: HR, 1.02 [95% CI, 0.77-1.35]; severe: HR, 0.74 [95% CI, 0.62-0.87]). In the context of stroke type, higher frequency of rehabilitation therapy was associated with reduced mortality rates compared with no rehabilitation therapy only in patients with hemorrhagic stroke (ischemic: HR, 1.04 [95% CI, 0.91-1.18]; hemorrhagic: HR, 0.60 [95% CI, 0.49-0.74])., Conclusions: We found a positive association between rehabilitation therapy within 6 months after stroke onset and long-term mortality in patients with stroke. A higher frequency of rehabilitation therapy would be recommended for poststroke patients, especially those with hemorrhagic stroke and severe disability., Competing Interests: None.

Chemiresistive gas sensors based on semiconducting metal oxides typically rely on noble metal catalysts to enhance their sensitivity and selectivity. However, noble metal catalysts have several drawbacks for practical utilization, including their high cost, their propensity for spontaneous agglomeration, and poisoning effects with certain types of gases. As such, in the interest of commercializing the chemiresistive gas sensor technology, we propose an alternative design for a noble-metal-free sensing material through the case study of Co-doped ceria (Co-CeO 2 ) catalysts embedded in a SnO 2 matrix. In this investigation, we utilized electrospinning and subsequent calcination to prepare Co-CeO 2 catalyst nanoparticles integrated with SnO 2 nanofibers (NFs) with uniform particle distribution and particle size regulation down to the sub-2 nm regime. The resulting Co-CeO 2 @SnO 2 NFs exhibited superior gas sensing characteristics toward isoprene (C 5 H 8 ) gas, a significant biomarker for monitoring the onset of various diseases through breath diagnostics. In particular, we identified that the Co-CeO 2 catalysts, owing to the transition metal doping, facilitated the spillover of chemisorbed oxygen species to the SnO 2 sensing body. This resulting in the sensor having a 27.4-fold higher response toward 5 ppm of C 5 H 8 (compared to pristine SnO 2 ), exceptionally high selectivity, and a low detection limit of 100 ppb. The sensor also exhibited high stability for prolonged response-recovery cycles, attesting to the strong anchoring of Co-CeO 2 catalysts in the SnO 2 matrix. Based on our findings, the transition metal-doped metal oxide catalysts, such as Co-CeO 2 , demonstrate strong potential to completely replace noble metal catalysts, thereby advancing the development of the commercially viable chemiresistive gas sensors free from noble metals, capable of detecting target gases at sub-ppm levels.

Objectives: Musclin, recently identified as a myokine, has been recognized for its physiological significance in potentiating the functional properties of natrieutic peptides (NPs) through competitive inhibition of their clearance receptor, natrieutic peptide receptor C (NPR-C). This study, for the first time in the literature, investigated the dynamic response of musclin during and after aerobic exercise in humans, exploring its potential as a myokine and its interaction with NPs and NPR-C in the context of exercise-induced metabolic responses., Methods: Twenty-one inactive young males participated, and we assessed changes in serum levels of musclin, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), epinephrine (Epi), and glycerol as an indicative of lipid mobilization, during and after moderate-intensity aerobic exercise. Furthermore, we evaluated the gene expression of NPR-C in subcutaneous fat biopsies., Results: Serum musclin levels increased significantly during aerobic exercise, followed by a decline during recovery, remaining elevated compared to baseline. Significant correlations were found between musclin responses and lean body mass (LBM), indicating its regulation by skeletal muscle mass and exercise. Exercise-induced changes in musclin positively correlated with those of ANP, potentially preventing ANP degradation. Additionally, a potential interplay between NPR-C expression and musclin dynamics on ANP was suggested. However, musclin's influence on lipid mobilization was not predominant when considering other lipolytic factors during exercise., Discussion: Musclin's classification as a myokine is supported by its response to aerobic exercise and its association with LBM. Additionally, its interactions with NPR-C and NPs suggest its physiological relevance and potential clinical implications., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

This study pioneers a chemical sensor based on surfactant-free aerosol-synthesized single-walled carbon nanotube (SWCNT) films for detecting nitrogen dioxide (NO 2 ). Unlike conventional CNTs, the SWCNTs used in this study exhibit one of the highest surface-to-volume ratios. They show minimal bundling without the need for surfactants and have the lowest number of defects among reported CNTs. Furthermore, the dry-transferrable and facile one-step lamination results in promising industrial viability. When applied to devices, the sensor shows excellent sensitivity (41.6% at 500 ppb), rapid response/recovery time (14.2/120.8 s), a remarkably low limit of detection (below ≈0.161 ppb), minimal noise, repeatability for more than 50 cycles without fluctuation, and long-term stability for longer than 6 months. This is the best performance reported for a pure CNT-based sensor. In addition, the aerosol SWCNTs demonstrate consistent gas-sensing performance even after 5000 bending cycles, indicating their suitability for wearable applications. Based on experimental and theoretical analyses, the proposed aerosol CNTs are expected to overcome the limitations associated with conventional CNT-based sensors, thereby offering a promising avenue for various sensor applications., (© 2024 Wiley‐VCH GmbH.)

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent condition in the general population. Although recent studies have demonstrated a link between NAFLD and lipoprotein(a), a low-density lipoprotein-like particle synthesized in the liver, its precise physiological role and mechanism of action remain unclear. This study aimed to investigate the relationship between lipoprotein(a) levels and development of NAFLD and hepatic fibrosis in Korean adults. A total of 1501 subjects who underwent abdominal ultrasonography at least twice as part of a health checkup program were enrolled. Biochemical and ultrasonography results were analyzed longitudinally, and the degree of hepatic fibrosis was calculated in subjects with NAFLD using serum biomarkers, such as fibrosis-4 (FIB-4). During the 3.36-year follow-up period, 352 patients (23.5%) were diagnosed with NAFLD. The subjects were categorized into 4 groups based on their lipoprotein(a) levels. Remarkably, the incidence of NAFLD decreased as the lipoprotein(a) levels increased. Following logistic regression analysis and adjustment for various risk factors, the odds ratio for the development of NAFLD was 0.625 (95% CI 0.440-0.888; P = .032) when comparing the highest to the lowest tertile of lipoprotein(a). However, no significant association was observed between the occurrence of hepatic fibrosis and lipoprotein(a) levels in subjects with NAFLD. Lipoprotein(a) levels have been identified as a significant predictor of NAFLD development. Additional large-scale studies with extended follow-up periods are required to better understand the effect of lipoprotein(a) on NAFLD and hepatic fibrosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Sleep has been known to affect childhood development. Sleep disturbance is likely more common in children with developmental delay (DD) than in typical development. There are few studies on the correlation between sleep disturbance and developmental features in children with DD. Therefore, this study aimed to evaluate the associations between the two in children with DD., Methods: A total of 45 children (age range 27.0 ± 11.1) with DD were recruited and evaluated using the Sleep Disturbance Scale for Children (SDSC) and Bayley Scales of Infant and Toddler Development (BSID-III). The outcomes are expressed as means and standard deviations. The correlation between SDSC and BSID-III was assessed using Spearman's rank correlation test. Multiple regression analysis was performed to investigate the relationship between BSID-III domains and SDSC questionnaire subscales. Statistical significance was set at p < 0.05., Results: Based on the correlation analysis and subsequent hierarchical regression analysis, cognition and socio-emotional domains of BSID-III were significantly associated with the DOES subscale of the SDSC questionnaire. In addition, the expressive language domain of the BSID-III was found to be associated with the DA subscale of the SDSC questionnaire. It seems that excessive daytime sleepiness might negatively affect emotional and behavioral problems and cognitive function. Also, arousal disorders seem to be related to memory consolidation process, which is thought to affect language expression., Conclusion: This study demonstrated that DA and DOES subscales of the SDSC questionnaire were correlated with developmental aspects in preschool-aged children with DD. Sleep problems in children with DD can negatively affect their development, thereby interfering with the effectiveness of rehabilitation. Identifying and properly managing the modifiable factors of sleep problems is also crucial as a part of comprehensive rehabilitation treatment. Therefore, we should pay more attention to sleep problems, even in preschool-aged children with DD., (© 2024. The Author(s).)

Background: Mechanical power (MP), the rate of mechanical energy (ME) delivery, is a recently introduced unifying ventilator parameter consisting of tidal volume, airway pressures, and respiratory rates, which predicts pulmonary complications in several clinical contexts. However, ME has not been previously studied in the perioperative context, and neither parameter has been studied in the context of thoracic surgery utilizing one-lung ventilation., Methods: The relationships between ME variables and postoperative pulmonary complications were evaluated in this post hoc analysis of data from a multicenter randomized clinical trial of lung resection surgery conducted between 2020 and 2021 (n = 1,170). Time-weighted average MP and ME (the area under the MP time curve) were obtained for individual patients. The primary analysis was the association of time-weighted average MP and ME with pulmonary complications within 7 postoperative days. Multivariable logistic regression was performed to examine the relationships between energy variables and the primary outcome., Results: In 1,055 patients analyzed, pulmonary complications occurred in 41% (431 of 1,055). The median (interquartile ranges) ME and time-weighted average MP in patients who developed postoperative pulmonary complications versus those who did not were 1,146 (811 to 1,530) J versus 924 (730 to 1,240) J (P < 0.001), and 6.9 (5.5 to 8.7) J/min versus 6.7 (5.2 to 8.5) J/min (P = 0.091), respectively. ME was independently associated with postoperative pulmonary complications (ORadjusted, 1.44 [95% CI, 1.16 to 1.80]; P = 0.001). However, the association between time-weighted average MP and postoperative pulmonary complications was time-dependent, and time-weighted average MP was significantly associated with postoperative pulmonary complications in cases utilizing longer periods of mechanical ventilation (210 min or greater; ORadjusted, 1.46 [95% CI, 1.11 to 1.93]; P = 0.007). Normalization of ME and time-weighted average MP either to predicted body weight or to respiratory system compliance did not alter these associations., Conclusions: ME and, in cases requiring longer periods of mechanical ventilation, MP were independently associated with postoperative pulmonary complications in thoracic surgery., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Dysregulation of cancer cell motility is a key driver of invasion and metastasis. High dysadherin expression in cancer cells is correlated with invasion and metastasis. Here, we found the molecular mechanism by which dysadherin regulates the migration and invasion of colon cancer (CC). Comprehensive analysis using single-cell RNA sequencing data from CC patients revealed that high dysadherin expression in cells is linked to cell migration-related gene signatures. We confirmed that the deletion of dysadherin in tumor cells hindered local invasion and distant migration using in vivo tumor models. In this context, by performing cell morphological analysis, we found that aberrant cell migration resulted from impaired actin dynamics, focal adhesion turnover and protrusive structure formation upon dysadherin expression. Mechanistically, the activation of focal adhesion kinase (FAK) was observed in dysadherin-enriched cells. The dysadherin/FAK axis enhanced cell migration and invasion by activating the FAK downstream cascade, which includes the Rho family of small GTPases. Overall, this study illuminates the role of dysadherin in modulating cancer cell migration by forcing actin dynamics and protrusive structure formation via FAK signaling, indicating that targeting dysadherin may be a potential therapeutic strategy for CC patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The global energy crisis caused by the overconsumption of nonrenewable fuels has prompted researchers to develop alternative strategies for producing electrical energy. In this review, a fascinating strategy that simply utilizes water, an abundant natural substance throughout the globe and even in air as moisture, as a power source is introduced. The concept of the hydrovoltaic electricity generator (HEG) proposed herein involves generating an electrical potential gradient by exposing the two ends of the HEG device to dissimilar physicochemical environments, which leads to the production of an electrical current through the active material. HEGs, with a large variety of viable active materials, have much potential for expansion toward diverse applications including permanent and/or emergency power sources. In this review, representative HEGs that generate electricity by the mechanisms of diffusion, streaming, and capacitance as case studies for building a fundamental understanding of the electricity generation process are discussed. In particular, by comparing the use and absence of hygroscopic materials, HEG mechanism studies to establish active material design principles are meticulously elucidated. The review with future perspectives on electrode design using conducting nanomaterials, considerations for high performance device construction, and potential impacts of the HEG technology in improving the livelihoods are reviewed., (© 2023 Wiley‐VCH GmbH.)

Objective: The aim of this study was to investigate the role of the follistatin-like 1 (Fstl1) and disco-interacting protein 2 homolog A (DIP2a) axis in relation to lipid metabolism during and after endurance exercise and to elucidate the mechanisms underlying the metabolic effects of Fstl1 on adipocytes, considering its regulation by exercise and muscle mass and its link to obesity., Methods: Twenty-nine sedentary males participated in endurance exercise, and blood samples were collected during and after the exercise. Body composition, Fstl1, glycerol, epinephrine, growth hormone, and atrial natriuretic peptide were measured. 3T3-L1 adipocytes, with or without DIP2a knockdown, were treated with Fstl1 to assess glycerol release, cyclic AMP/cyclic GMP production, and hormone sensitive lipase phosphorylation. The association between DIP2a gene expression levels in human adipose tissues and exercise-induced lipolysis was examined., Results: Fstl1 levels significantly increased during endurance exercise and following recovery, correlating with lean body mass and lipolysis. In 3T3-L1 adipocytes, Fstl1 increased glycerol release, cyclic GMP production, and hormone sensitive lipase activation, but these effects were attenuated by DIP2a knockdown. DIP2a gene expression in human adipose tissues correlated with serum glycerol concentrations during endurance exercise., Conclusions: Fstl1 is a myokine facilitating lipid mobilization during and after endurance exercise through DIP2a-mediated lipolytic effects in adipocytes., (© 2023 The Obesity Society.)

Objective: To investigate the feasibility and effects of a mobile app-based home cycling exercise program compared to home cycling exercise without additional monitoring system. Compared with fitness facilities or outdoor exercise, home-based exercise programs effectively improve physical performance in an indwelling community. However, a flexible, informal environment may decrease motivation and impair adherence to physical exercise. Mobile devices for aerobic exercise and mobile applications provide real-time monitoring, immediate feedback, and encouragement to increase motivation and promote physical performance. We investigated the feasibility and effects of a mobile app-based home exercise program on body composition, muscular strength, and cardiopulmonary function., Methods: Between February and May 2023, 20 participants were randomly allocated to the intervention (mobile application with a tablet) and control groups, and they performed aerobic exercise using a stationary bicycle for ≥150 minutes per week for 6 weeks (≤30-minute exercise session, with 3-minute warm-up and 3-minute cool-down). Karvonen formula-based heartrate defined the weekly increase in exercise intensity. Outcome measures included body-composition parameters, isokinetic knee flexor and extensor strength tests, cardiopulmonary exercise test results, and rate of target heart rate (HR) achievement. Participants were assessed at baseline and after the intervention., Results: Unrelated personal events led two participants to drop out. The intervention and control groups had similar baseline characteristics. Compared with the control group, in the post-intervention isokinetic strength test, bilateral knee flexor and extensor power, and time to target HR achievement significantly increased each week in the intervention group., Conclusion: Home-based exercise to achieve long-term cardiovascular fitness with portable electronic/mobile devices facilitates individualized exercise using real-time feedback to improve motivation and adherence.

Respiratory masks are the primary and most effective means of protecting individuals from airborne hazards such as droplets and particulate matter during public engagements. However, conventional electrostatically charged melt-blown microfiber masks typically require thick and dense membranes to achieve high filtration efficiency, which in turn cause a significant pressure drop and reduce breathability. In this study, we have developed a multielectrospinning system to address this issue by manipulating the pore structure of nanofiber networks, including the use of uniaxially aligned nanofibers created via an electric-field-guided electrospinning apparatus. In contrast to the common randomly collected microfiber membranes, partially aligned dual-nanofiber membranes, which are fabricated via electrospinning of a random 150 nm nanofiber base layer and a uniaxially aligned 450 nm nanofiber spacer layer on a roll-to-roll collector, offer an efficient way to modulate nanofiber membrane pore structures. Notably, the dual-nanofiber configuration with submicron pore structure exhibits increased fiber density and decreased volume density, resulting in an enhanced filtration efficiency of over 97% and a 50% reduction in pressure drop. This leads to the highest quality factor of 0.0781. Moreover, the submicron pore structure within the nanofiber networks introduces an additional sieving filtration mechanism, ensuring superior filtration efficiency under highly humid conditions and even after washing with a 70% ethanol solution. The nanofiber mask provides a sustainable solution for safeguarding the human respiratory system, as it effectively filters and inactivates human coronaviruses while utilizing 130 times fewer polymeric materials than melt-blown filters. This reusability of our filters and their minimum usage of polymeric materials would significantly reduce plastic waste for a sustainable global society.

Natural products are continuously being researched to develop safe and effective treatment options for cervical cancer, the fourth most common cancer in women. Piperlongumine (PL), an amide alkaloid mainly present in long pepper, exhibits neuroprotective and anti-cancer properties. However, the specific effect of PL in cervical cancer and the relationship between the anti-cancer pathway and autophagy remain unclear. Therefore, we aimed to investigate PL-induced apoptosis in KB human cervical cancer cells and the relationship between apoptosis and autophagy therein. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and wound-healing assays showed that PL treatment suppressed KB cell viability and proliferation. Apoptosis was identified through 4',6-diamidino-2-phenylindole and annexin V-propidium iodide staining, increased cleaved-poly (ADP-ribose) polymerase and Bcl-2 associated X levels, and decreased B cell lymphoma 2 levels. Acridine orange staining and increased microtubule-associated protein 1A/1B-light chain 3-II and Beclin-1 levels confirmed autophagy. We determined that KB cell-related autophagy exerted cytoprotective effects using the autophagy inhibitors 3-methyladenine and hydroxychloroquine. PL treatment promoted apoptosis by inhibiting the phosphatidylinositol-3-kinase (PI3K)/protein kinase B/mammalian target of rapamycin pathway in KB cells; inhibiting the pathway using PI3K inhibitors increased autophagy. We suggest that PL is a potential natural anticancer agent for cervical cancer treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: To maintain adequate oxygenation is of utmost importance in intraoperative care. However, clinical evidence supporting specific oxygen levels in distinct surgical settings is lacking. This study aimed to compare the effects of 30% and 80% oxygen in off-pump coronary artery bypass grafting (OPCAB)., Methods: This multicenter trial was conducted in three tertiary hospitals from August 2019 to August 2021. Patients undergoing OPCAB were cluster-randomized to receive either 30% or 80% oxygen intraoperatively, based on the month when the surgery was performed. The primary endpoint was the length of hospital stay. Intraoperative hemodynamic data were also compared., Results: A total of 414 patients were cluster-randomized. Length of hospital stay was not different in the 30% oxygen group compared to the 80% oxygen group (median, 7.0 days vs 7.0 days; the sub-distribution hazard ratio, 0.98; 95% confidence interval [CI] 0.83-1.16; P = 0.808). The incidence of postoperative acute kidney injury was significantly higher in the 30% oxygen group than in the 80% oxygen group (30.7% vs 19.4%; odds ratio, 1.94; 95% CI 1.18-3.17; P = 0.036). Intraoperative time-weighted average mixed venous oxygen saturation was significantly higher in the 80% oxygen group (74% vs 64%; P < 0.001). The 80% oxygen group also had a significantly greater intraoperative time-weighted average cerebral regional oxygen saturation than the 30% oxygen group (56% vs 52%; P = 0.002)., Conclusions: In patients undergoing OPCAB, intraoperative administration of 80% oxygen did not decrease the length of hospital stay, compared to 30% oxygen, but may reduce postoperative acute kidney injury. Moreover, compared to 30% oxygen, intraoperative use of 80% oxygen improved oxygen delivery in patients undergoing OPCAB. Trial registration ClinicalTrials.gov (NCT03945565; April 8, 2019)., (© 2023. The Author(s).)

Autophagy has bidirectional functions in cancer by facilitating cell survival and death in a context-dependent manner. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are a large family of proteins essential for numerous biological processes, including autophagy; nevertheless, their potential function in cancer malignancy remains unclear. Here, we explored the gene expression patterns of SNAREs in tissues of patients with colorectal cancer (CRC) and discovered that SEC22B expression, a vesicle SNARE, was higher in tumor tissues than in normal tissues, with a more significant increase in metastatic tissues. Interestingly, SEC22B knockdown dramatically decreased CRC cell survival and growth, especially under stressful conditions, such as hypoxia and serum starvation, and decreased the number of stress-induced autophagic vacuoles. Moreover, SEC22B knockdown successfully attenuated liver metastasis in a CRC cell xenograft mouse model, with histological signs of decreased autophagic flux and proliferation within cancer cells. Together, this study posits that SEC22B plays a crucial role in enhancing the aggressiveness of CRC cells, suggesting that SEC22B might be an attractive therapeutic target for CRC., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jeong-Seok Nam reports financial support was provided by the National Research Foundation of Korea through a grant funded by the Korean government and by Gwangju Institute of Science and Technology (GIST)., (Copyright © 2023. Published by Elsevier Inc.)

The unorthodox surface chemistry of high-entropy alloy nanoparticles (HEA-NPs), with numerous interelemental synergies, helps catalyze a variety of essential chemical processes, such as the conversion of CO 2 to CO, as a sustainable path to environmental remediation. However, the risk of agglomeration and phase separation in HEA-NPs during high-temperature operations are lasting issues that impede their practical viability. Herein, we present HEA-NP catalysts that are tightly sunk in an oxide overlayer for promoting the catalytic conversion of CO 2 with exceptional stability and performance. We demonstrated the controlled formation of conformal oxide overlayers on carbon nanofiber surfaces via a simple sol-gel method, which facilitated a large uptake of metal precursor ions and helped to decrease the reaction temperature required for nanoparticle formation. During the rapid thermal shock synthesis process, the oxide overlayer would also impede nanoparticle growth, resulting in uniformly distributed small HEA-NPs (2.37 ± 0.78 nm). Moreover, these HEA-NPs were firmly socketed in the reducible oxide overlayer, enabling an ultrastable catalytic performance involving >50% CO 2 conversion with >97% selectivity to CO for >300 h without extensive agglomeration. Altogether, we establish the rational design principles for the thermal shock synthesis of high-entropy alloy nanoparticles and offer a helpful mechanistic perspective on how the oxide overlayer impacts the nanoparticle synthesis behavior, providing a general platform for the designed synthesis of ultrastable and high-performance catalysts that could be utilized for various industrially and environmentally relevant chemical processes.

Background: Allergic inflammation affects the epithelial cell populations resulting in goblet cell hyperplasia and decreased ciliated cells. Recent advances in single-cell RNA sequencing (scRNAseq) have enabled the identification of new cell subtypes and genomic features of single cells. In this study, we aimed to investigate the effect of allergic inflammation in nasal epithelial cell transcriptomes at the single-cell level., Methods: We performed scRNAseq in cultured primary human nasal epithelial (HNE) cells and in vivo nasal epithelium. The transcriptomic features and epithelial cell subtypes were determined under IL-4 stimulation, and cell-specific marker genes and proteins were identified., Results: We confirmed that cultured HNE cells were similar to in vivo epithelial cells through scRNAseq. Cell-specific marker genes were utilized to cluster the cell subtypes, and FOXJ1 + -ciliated cells were sub-classified into multiciliated and deuterosomal cells. PLK4 and CDC20B were specific for deuterosomal cells, and SNTN, CPASL, and GSTA2 were specific for multiciliated cells. IL-4 altered the proportions of cell subtypes, resulting in a decrease in multiciliated cells and loss of deuterosomal cells. The trajectory analysis revealed deuterosomal cells as precursor cells of multiciliated cells and deuterosomal cells function as a bridge between club and multiciliated cells. A decrease in deuterosomal cell marker genes was observed in nasal tissue samples with type 2 inflammation., Conclusion: The effects of IL-4 appear to be mediated through the loss of the deuterosomal population, resulting in the reduction in multiciliated cells. This study also newly suggests cell-specific markers that might be pivotal for investigating respiratory inflammatory diseases., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Predicting the survival of cancer patients provides prognostic information and therapeutic guidance. However, improved prediction models are needed for use in diagnosis and treatment., Objective: This study aimed to identify genomic prognostic biomarkers related to colon cancer (CC) based on computational data and to develop survival prediction models., Methods: We performed machine-learning (ML) analysis to screen pathogenic survival-related driver genes related to patient prognosis by integrating copy number variation and gene expression data. Moreover, in silico system analysis was performed to clinically assess data from ML analysis, and we identified RABGAP1L, MYH9, and DRD4 as candidate genes. These three genes and tumor stages were used to generate survival prediction models. Moreover, the genes were validated by experimental and clinical analyses, and the theranostic application of the survival prediction models was assessed., Results: RABGAP1L, MYH9, and DRD4 were identified as survival-related candidate genes by ML and in silico system analysis. The survival prediction model using the expression of the three genes showed higher predictive performance when applied to predict the prognosis of CC patients. A series of functional analyses revealed that each knockdown of three genes reduced the protumor activity of CC cells. In particular, validation with an independent cohort of CC patients confirmed that the coexpression of MYH9 and DRD4 gene expression reflected poorer clinical outcomes in terms of overall survival and disease-free survival., Conclusions: Our survival prediction approach will contribute to providing information on patients and developing a therapeutic strategy for CC patients., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Myocardial systolic longitudinal function has been known to decrease in patients with severe aortic stenosis (AS). Preoperative peak systolic myocardial velocity at the septal mitral valve annulus (S'), measured using Doppler tissue imaging, was used as an indicator for myocardial systolic longitudinal function. The prognostic value and natural course of S' after surgical aortic valve replacement for severe AS have not been elucidated. This retrospective observational study included patients from January 2006 to December 2018. The patients were divided to 2 groups (pre-S' HIGH vs. pre-S' LOW ) with a cut-off 5.4 cm/s of preoperative S' (pre-S') that was identified by restricted cubic spline curve. The primary outcome was postoperative long-term all-cause mortality. Nine hundred and five patients were analyzed. All-cause mortality rate at the median follow-up period of 5.2 years was 12% in pre-S' LOW and 8% in pre-S' HIGH . Multivariate analysis showed that pre-S' LOW was associated with an increased all-cause mortality (hazard ratio, 1.60; 95% confidence interval, 1.04-2.48; P = 0.032). Significantly different trajectories of postoperative S' (post-S') were found between two groups (P < 0.001 for difference): In pre-S' LOW , post-S' increased within 6 months after surgery, and gradually decreased over time, whereas it slowly decreased up to 5 years after surgery and then reached a plateau in pre-S' HIGH. The difference in pre-S' level maintained over time, and remained consistent in the adjusted analysis. Pre-S' < 5.4 cm/s was found to be associated with an increased long-term all-cause mortality. In addition, the trajectories for post-S' were different according to pre-S', which remained after adjustment., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Airway driving pressure, easily measured as plateau pressure minus PEEP, is a surrogate for alveolar stress and strain. However, the effect of its targeted reduction remains unclear., Methods: In this multicentre trial, patients undergoing lung resection surgery were randomised to either a driving pressure group (n=650) receiving an alveolar recruitment/individualised PEEP to deliver the lowest driving pressure or to a conventional protective ventilation group (n=650) with fixed PEEP of 5 cm H 2 O. The primary outcome was a composite of pulmonary complications within 7 days postoperatively., Results: The modified intention-to-treat analysis included 1170 patients (mean [standard deviation, sd]; age, 63 [10] yr; 47% female). The mean driving pressure was 7.1 cm H 2 O in the driving pressure group vs 9.2 cm H 2 O in the protective ventilation group (mean difference [95% confidence interval, CI]; -2.1 [-2.4 to -1.9] cm H 2 O; P<0.001). The incidence of pulmonary complications was not different between the two groups: driving pressure group (233/576, 40.5%) vs protective ventilation group (254/594, 42.8%) (risk difference -2.3%; 95% CI, -8.0% to 3.3%; P=0.42). Intraoperatively, lung compliance (mean [sd], 42.7 [12.4] vs 33.5 [11.1] ml cm H 2 O -1 ; P<0.001) and Pa o2 (median [inter-quartile range], 21.5 [14.5 to 30.4] vs 19.5 [13.5 to 29.1] kPa; P=0.03) were higher and the need for rescue ventilation was less frequent (6.8% vs 10.8%; P=0.02) in the driving pressure group., Conclusions: In lung resection surgery, a driving pressure-guided ventilation improved pulmonary mechanics intraoperatively, but did not reduce the incidence of postoperative pulmonary complications compared with a conventional protective ventilation., Clinical Trial Registration: NCT04260451., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To evaluate the incremental prognostic value of longitudinal strain over left ventricular ejection fraction (LVEF) after coronary artery bypass grafting (CABG)., Design: Retrospective cohort study., Setting: Single tertiary-care center., Participants: Patients underwent isolated CABG between January 2014 and December 2019., Interventions: None., Measurements and Main Results: There were 999 patients (median age, 65 years, 23.5% female) categorized into 3 groups according to their left ventricular (LV) systolic function status: pEF/pS (preserved LVEF and preserved longitudinal strain, n = 490), pEF/iS (preserved LVEF and impaired longitudinal strain, n = 186), and rEF (reduced LVEF, n = 323). During a median follow-up of 2.7 years, 86 (8.6%) patients had died. The 5-year survival significantly differed in patients with preserved LVEF according to the strain status (pEF/pS v pEF/iS, 90.0% v 84.6%; p = 0.002). After adjusting for potential confounders, the pEF/iS group (adjusted hazard ratio [HR], 2.17; 95% CI, 1.10-4.28; p = 0.03) and the rEF group (adjusted HR, 2.96; 95% CI, 1.46-6.00; p = 0.003) had significantly higher risks for all-cause death compared with the pEF/pS group. The addition of longitudinal strain to LVEF in the prediction model significantly improved its performance (global chi-squared, 105.2 v 110.2; p = 0.03)., Conclusions: Left ventricular longitudinal strain could differentiate the prognosis after CABG in patients with preserved LVEF and provide significant incremental prognostic value to LVEF., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Reversible thiol-disulfide exchange chemistry is of particular interest in drug delivery systems. However, high levels of glutathione (GSH) in cancer cells are hard to distinguish from GSH in normal cells, resulting in unmanageable cytotoxic drug release. This study investigates the spatiotemporally-controlled irreversible degradation of Ir-based photosensitizer (TIr3)-encapsulating nanogels (IrNG) through the hyperoxidation of resulting intracellular thiols using reactive oxygen species (ROS). A highly cytotoxic TIr3 was stably encapsulated within IrNG through hydrophobic interactions and reversible crosslinking between its disulfide bonds and thiols in the absence of light, resulting in high biocompatibility under normal cellular conditions. However, upon photoirradiation, TIr3 generated high levels of ROS, irreversibly oxidizing the thiols to induce electrostatic repulsion between the polymer molecules, resulting in the TIr3 release and induction of cancer cell apoptosis., (© 2022 Wiley-VCH GmbH.)

Background: The effects of specific body mass index (BMI) category and sarcopenia within each BMI category on outcomes in patients undergoing esophageal surgery with esophageal squamous cell carcinoma have not been thoroughly examined., Methods: This study included 1141 patients. Sarcopenia was determined with a total psoas muscle cross-sectional area at the level of the third lumbar vertebra in computed tomography. The outcomes were long-term survival, including overall survival (OS) and recurrence-free survival (RFS), and postoperative complications., Results: The overweight and no sarcopenia group was considered as the reference. After adjusting covariates, the underweight and the normal weight and sarcopenia groups both showed worse OS (underweight group: hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.33-3.13, p = 0.001; normal weight and sarcopenia group: HR 1.93, 95% CI 1.39-2.69, p < 0.001) and worse RFS (underweight group: HR 1.78, 95% CI 1.19-2.67, p = 0.005; normal weight and sarcopenia group: HR 1.70, 95% CI 1.25-2.30, p = 0.001). In addition, the underweight group (odds ratio [OR] 4.74, 95% CI 2.05-10.96, p < 0.001), the normal weight and sarcopenia group (OR 3.26, 95% CI 1.60-6.62, p = 0.001), the overweight and sarcopenia group (OR 2.54, 95% CI 1.14-5.68, p = 0.023), and the obese and no sarcopenia group (OR 2.44, 95% CI 1.14-5.22, p = 0.021) were at significantly higher risk of postoperative 30-day composite complications., Conclusions: Compared with the overweight and no sarcopenia group, the underweight and the normal weight and sarcopenia groups were associated with worse short- and long-term outcomes., (© 2022. Society of Surgical Oncology.)

Background: Left ventricular longitudinal strain is an emerging marker of ventricular systolic function. However, the prognostic value of apical four-chamber longitudinal strain after heart valve surgery in real-world clinical practice is uncertain. The authors investigated whether left ventricular apical four-chamber longitudinal strain measured in real-world practice is helpful for predicting postoperative outcomes in patients undergoing heart valve surgery., Methods: This observational cohort study was conducted in patients who underwent heart valve surgery between January 2014 and December 2018 at a tertiary hospital in South Korea. The exposure of interest was preoperative left ventricular apical four-chamber longitudinal strain. The primary outcome was postoperative all-cause mortality., Results: Among 1,773 study patients (median age, 63 years; female, 45.9%), 132 (7.4%) died during a median follow-up of 27.2 months. Preoperative left ventricular apical four-chamber longitudinal strain was significantly associated with all-cause mortality (adjusted hazard ratio, 0.94 per 1% increment in absolute value; 95% CI [0.90, 0.99], P = 0.022), whereas left ventricular ejection fraction (LVEF) was not significantly associated with all-cause mortality (adjusted hazard ratio: 1.01, 95% CI [0.99, 1.03], P = 0.222). Moreover, combining left ventricular apical four-chamber longitudinal strain to the LVEF and conventional prognostic factors enhance the prognostic model for all-cause mortality (P = 0.022)., Conclusions: In patients undergoing heart valve surgery without coronary artery disease, left ventricular apical four-chamber longitudinal strain measured in real-world clinical practice was independently associated with postoperative survival. Left ventricular longitudinal strain measurement may be helpful for outcome prediction after valve surgery.

Aortic stenosis (AS) is the second most common valvular heart disease in the United States. Although the prevalence of AS does not significantly differ between the sexes, there is some controversy on whether sex differences affect the long-term mortality of patients with severe AS undergoing surgical aortic valve replacement (SAVR). Therefore, we retrospectively analyzed the medical records of 917 patients (female, n = 424 [46.2%]) with severe AS who had undergone isolated SAVR at a tertiary care center between January 2005 and December 2018. During a median follow-up of 5.2 years, 74 (15.0%) male patients and 41 (9.7%) female patients died. The Kaplan-Meier analysis revealed that the 10-year mortality rate was significantly higher in male than female patients (24.7% vs. 17.9%, log-rank p = 0.005). In the sequential Cox proportional hazard regression model for assessing long-term mortality up to 10 years post-surgery, the adjusted hazard ratio of male sex for mortality was 1.93 (95% confidence interval, 1.28-2.91; p = 0.002). The association between male sex and postoperative long-term mortality was not significantly diminished by any demographic or clinical factor in subgroup analyses. In conclusion, female sex was significantly associated with better long-term survival in patients with severe AS undergoing SAVR.

As an enveloped virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delivers its viral genome into host cells via fusion of the viral and cell membranes. Here, we show that ANO6/TMEM16F-mediated cell surface exposure of phosphatidylserine is critical for SARS-CoV-2 entry and that ANO6-selective inhibitors are effective against SARS-CoV-2 infections. Application of the SARS-CoV-2 Spike pseudotyped virus (SARS2-PsV) evokes a cytosolic Ca 2+ elevation and ANO6-dependent phosphatidylserine externalization in ACE2/TMPRSS2-positive mammalian cells. A high-throughput screening of drug-like chemical libraries identifies three different structural classes of chemicals showing ANO6 inhibitory effects. Among them, A6-001 displays the highest potency and ANO6 selectivity and it inhibits the single-round infection of SARS2-PsV in ACE2/TMPRSS2-positive HEK 293T cells. More importantly, A6-001 strongly inhibits authentic SARS-CoV-2-induced phosphatidylserine scrambling and SARS-CoV-2 viral replications in Vero, Calu-3, and primarily cultured human nasal epithelial cells. These results provide mechanistic insights into the viral entry process and offer a potential target for pharmacological intervention to protect against coronavirus disease 2019 (COVID-19)., Competing Interests: Declaration of interests M.G.L., J.M.L., and W.N. are inventors on a pending patent related to this work filed by Yonsei University Office of Research Affairs/University Industry Foundation. The authors declare no other competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Rationale: Doublecortin-like kinase 1 (DCLK1) is a serine/threonine kinase that selectively marks cancer stem-like cells (CSCs) and promotes malignant progression in colorectal cancer (CRC). However, the exact molecular mechanism by which DCLK1 drives the aggressive phenotype of cancer cells is incompletely determined. Methods: Here, we performed comprehensive genomics and proteomics analyses to identify binding proteins of DCLK1 and discovered X-ray repair cross-complementing 5 (XRCC5). Thus, we explored the biological role and downstream events of the DCLK1/XRCC5 axis in human CRC cells and CRC mouse models. Results: The results of comprehensive bioinformatics analyses suggested that DCLK1-driven CRC aggressiveness is linked to inflammation. Mechanistically, DCLK1 bound and phosphorylated XRCC5, which in turn transcriptionally activated cyclooxygenase-2 expression and enhanced prostaglandin E 2 production; these events collectively generated the inflammatory tumor microenvironment and enhanced the aggressive behavior of CRC cells. Consistent with the discovered mechanism, inhibition of DCLK1 kinase activity strongly impaired the tumor seeding and growth capabilities in CRC mouse models. Conclusion: Our study illuminates a novel mechanism that mediates the pro-inflammatory function of CSCs in driving the aggressive phenotype of CRC, broadening the biological function of DCLK1 in CRC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)