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Background and Aims: Cancer-associated fibroblasts (CAFs) play key roles in the tumor microenvironment. IgA contributes to inflammation and dismantling antitumor immunity in the human liver. In this study, we aimed to elucidate the effects of the IgA complex on CAFs in Pil Soo Sung the tumor microenvironment of HCC., Approach and Results: CAF dynamics in HCC tumor microenvironment were analyzed through single-cell RNA sequencing of HCC samples. CAFs isolated from 50 HCC samples were treated with mock or serum-derived IgA dimers in vitro. Progression-free survival of patients with advanced HCC treated with atezolizumab and bevacizumab was significantly longer in those with low serum IgA levels ( p <0.05). Single-cell analysis showed that subcluster proportions in the CAF-fibroblast activation protein-α matrix were significantly increased in patients with high serum IgA levels. Flow cytometry revealed a significant increase in the mean fluorescence intensity of fibroblast activation protein in the CD68 + cells from patients with high serum IgA levels ( p <0.001). We confirmed CD71 (IgA receptor) expression in CAFs, and IgA-treated CAFs exhibited higher programmed death-ligand 1 expression levels than those in mock-treated CAFs ( p <0.05). Coculture with CAFs attenuated the cytotoxic function of activated CD8 + T cells. Interestingly, activated CD8 + T cells cocultured with IgA-treated CAFs exhibited increased programmed death-1 expression levels than those cocultured with mock-treated CAFs ( p <0.05)., Conclusions: Intrahepatic IgA induced polarization of HCC-CAFs into more malignant matrix phenotypes and attenuates cytotoxic T-cell function. Our study highlighted their potential roles in tumor progression and immune suppression., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background: Extracranial vascular malformations affect vessel inflammation, clotting, and ischemia. However, the relationship between extracranial vascular malformations and myocardial infarction (MI) or stroke has not been fully elucidated. Limited studies have investigated the association between extracranial vascular malformations and cardiovascular diseases., Methods: A total of 48,701 patients with extracranial vascular malformations and a control cohort of 487,010 age- and sex-matched participants from the Korean National Health Insurance database were included. The incidence and risk of MI, ischemic stroke (IS), and hemorrhagic stroke (HS) between participants with extracranial vascular malformations and the control cohort was compared., Results: After adjusting for other cardiovascular disease risk factors, the adjusted hazard ratios (aHRs) for venous malformations, capillary malformations (CMs), arteriovenous malformations (AVMs), and lymphatic malformations in patients with acute MI were 1.25 (CI, 1.04 to 1.50), 1.41 (CI, 1.24 to 1.61), 1.68 (CI, 1.18 to 2.37), and 1.40 (CI, 1.31 to 1.48), respectively. For IS, the aHRs were 1.55 (CI, 1.35 to 1.77), 1.92 (CI, 1.74 to 2.11), 1.13 (CI, 0.78 to 1.64), and 1.51 (CI, 1.44 to 1.58), respectively. For HS, the aHRs were 1.51 (CI, 1.12 to 2.05), 5.63 (CI, 4.97 to 6.38), 2.93 (CI, 1.82 to 4.72), and 1.34 (CI, 1.20 to 1.50), respectively., Conclusions: Independent of cardiovascular risk factors, extracranial vascular malformations were associated with an increased risk of MI, IS, and HS. For patients with CMs and AVMs, intracerebral hemorrhage risk was particularly high, accounting for 563% and 293%, respectively. Therefore, even in patients with extracranial CMs or AVMs, performing diagnostic evaluations for cerebral AVMs and using measures to prevent intracerebral hemorrhage are crucial., Clinical Question/level of Evidence: Risk, II., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons.)

Background: Various surgical methods have been developed for treating velopharyngeal insufficiency (VPI); however, the choice of surgical treatment is controversial. The pharyngeal flap, which is commonly used, has a high success rate but frequently leads to airway complications. Furlow double-opposing Z-plasty (DOZ) does not deform the velopharyngeal port; therefore, it is expected to show good speech outcomes while reducing airway complications if an appropriate indication is noted. This study aimed to identify indications for DOZ in cases of VPI after palatoplasty., Methods: Nonsyndromic patients who underwent palatoplasty were prospectively followed from 2008 to 2016, and those diagnosed with VPI were treated with DOZ. Preoperative facial computed tomography (CT) and postoperative nasometric assessment results were examined. Surgical indication was set based on a 30% threshold value for postoperative nasalance., Results: Comparing the preoperative CT measurements of both groups, high need ratio (NR), wide width of the nasopharynx (WNP), and long velopharyngeal depth (VPD) were contributing factors to VPI occurrence ( P < 0.05). Analyzing preoperative CT and postoperative speech evaluation results, a linear relationship was observed between preoperative NR, WNP, and VPD and postoperative nasalance. In cases where NR was less than 0.81, WNP was less than 27.64 mm, and VPD was less than 20.34 mm, DOZ showed favorable outcomes ( P < 0.05)., Conclusions: Preoperative CT evaluation should be performed in patients with VPI. When WNP, VPD, and NR values are small, DOZ can achieve sufficient correction of VPI and reduce the risk of airway complications. In cases where the indication range is exceeded, the pharyngeal flap is considered., Clinical Question/level of Evidence: Risk, III., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Lateral flow assays (LFAs) are a cost-effective and rapid colorimetric technology that can be effectively used for nucleic acid tests (NATs) in various fields such as medical diagnostics and biotechnology. Given their importance, developing more diverse LFAs that operate through novel working mechanisms is essential for designing highly selective and sensitive NATs and providing insights for designing various practical point-of-care testing (POCT) systems. Herein we report a new type of lateral flow assay (LFA) based on fluorescein-switching, enabled by nucleic acid-templated photooxidation of reduced fluorescein by riboflavin tetraacetate (RFTA). The LFA design leverages the fact that a reduced form of fluorescein, which weakly binds to gold nanoparticle (GNP)-conjugated anti-fluorescein antibodies, is oxidized in the presence of target nucleic acids to yield its native state, which then strongly binds to the antibodies. The study involved designing and optimizing probe sequences to detect miR-6090 and miR-141, which are significant markers for prostate cancer. To minimize background signals of LFAs, sodium borohydride (NaBH 4 ) was specifically introduced as a reducing agent, and detailed procedures were established. The developed LFA system accurately identified low fmol levels of target microRNAs with minimal false positives, all detectable with the naked eye, making the system a promising tool for point-of-care diagnostics.

This study provides a thorough examination of the important intersection of Wireless Sensor Networks (WSNs) with machine learning (ML) for improving security. WSNs play critical roles in a wide range of applications, but their inherent constraints create unique security challenges. To address these problems, numerous ML algorithms have been used to improve WSN security, with a special emphasis on their advantages and disadvantages. Notable difficulties include localisation, coverage, anomaly detection, congestion control, and Quality of Service (QoS), emphasising the need for innovation. This study provides insights into the beneficial potential of ML in bolstering WSN security through a comprehensive review of existing experiments. This study emphasises the need to use ML's potential while expertly resolving subtle nuances to preserve the integrity and dependability of WSNs in the increasingly interconnected environment.

Background/aim: Epithelial ovarian cancer (EOC) is a lethal disease that is the fifth leading cause of cancer-related death in women. BAF312 (siponimod) is a potent and selective sphingosine-1-phosphate (S1P) receptor modulator that has been approved as a treatment for multiple sclerosis. In addition to its immunomodulatory action, BAF312 shows preclinical antitumor effects in several cancer types. This study sought to determine whether BAF312 had anticancer properties against EOC using in vitro and in vivo models., Materials and Methods: EOC cell lines A2780, SKOV3ip1, A2780-CP20, and SKOV3-TR were treated with BAF312 and tested for cell proliferation, apoptosis, and migration using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, fluorescence-activated cell sorting, and migration assays. We investigated the expression of sphingosine-1-phosphate receptor 1 (S1PR1) in most EOC cell lines through western blot analysis. To investigate potential mechanisms, western blot analysis was used to assess the expression of AKT serine/threonine kinase 1 (AKT) and extracellular-regulated kinase (ERK) after BAF312 treatment. We also created poly(D,L-lactide-co-glycolide) nanoparticles encapsulating BAF312 (PLGA-NP-BAF312) for in vivo therapy. The average size and zeta potential of PLGA-NP-BAF312 were determined using dynamic light scattering. The therapeutic efficacy of PLGA-NP-BAF312 was tested in an A2780 tumor-bearing orthotopic mouse model of EOC., Results: S1PR1 was overexpressed in most EOC cell lines. BAF312 significantly reduced cell proliferation and migration while inducing significant apoptosis in all EOC cell lines. PLGA-NP-BAF312 treatment significantly reduced tumor weights in A2780 tumor-bearing mice. Furthermore, the anticancer effects of BAF312 were associated with reduced phosphorylation of ERK and AKT., Conclusion: Our findings show that BAF312 has significant anticancer effects in EOC cells by inhibiting the ERK and AKT pathways, and might potentially be used to treat EOCs., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Cerebral vasospasm (CVS) is an important contributor to delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage (aSAH), leading to high morbidity and long-term disability. While several microRNAs (miRNAs) have been implicated in vasospasm, the underlying mechanisms for CVS remain poorly understood. Our study aims to identify miRNAs that may contribute to the development of CVS. Whole-blood samples were obtained during or outside of vasospasm from aSAH patients whose maximal vasospasm was moderate or severe. MiRNAs were isolated from serial whole-blood samples, and miRNA sequencing was performed. Differentially expressed miRNAs were identified and the expression levels in patients' samples were verified using real-time qPCR. The biological functions of identified miRNA were evaluated in human brain endothelial cells (HBECs). MiRNA profiling revealed significant upregulation of miR-148b-3p in patients during CVS. We demonstrated that miR-148b-3p directly targeted and decreased the expression of ROCK1, affecting cell proliferation, migration, and invasion of HBECs through the ROCK-LIMK-Cofilin pathway. We propose that the upregulation of miRNA-148b-3p plays a role in the development of CVS by regulating actin cytoskeletal dynamics in HBECs, which is crucial for vascular function. Our study highlights miR-148b-3p as a potential diagnostic marker as well as therapeutic target for CVS following aSAH., (© 2024. The Author(s).)

An adaptive Nesterov quasi-Newton acceleration (an-QNA)-optimized low-noise amplifier (LNA) is proposed in this paper. An optimized single-ended-to-differential two-stage LNA circuit is presented. It includes an improved post-linearization (I PL ) technique to enhance the linearity. Traditional methods like conventional quasi-Newton (c-QN) often suffer from slow convergence and the tendency to get trapped in local minima. However, the proposed an-QNA method significantly accelerates the convergence speed. Furthermore, in this paper, modifications have been made to the an-QNA algorithm using a quadratic estimation to guarantee global convergence. The optimized an-QNA-based LNA, using standard 65 nm CMOS technology, achieves a simulated gain of 17.5 dB, a noise figure (NF) of 3.7 dB, and a 1 dB input compression point (IP 1 dB) of -13.1 dBm. It is also noted that the optimized LNA achieves a measured gain of 12.9 dB and an NF of 4.98 dB, and the IP 1 dB is -17.8 dB. The optimized LNA has a chip area of 0.67 mm 2 .

Objective: Ovarian cancer, a leading cause of cancer-related deaths in women, remains a formidable challenge, especially in the context of platinum-resistant disease. This study investigated the potential of the benzimidazole derivative BNZ-111 as a novel treatment strategy for platinum-resistant ovarian cancer., Methods: The human EOC cell lines A2780, HeyA8, SKOV3ip1, A2780-CP20, HeyA8-MDR, and SKOV3-TR were treated with BNZ-111, and cell proliferation, apoptosis, and cell cycle were assessed., Results: It demonstrated strong cytotoxicity in both chemo-sensitive and chemo-resistant epithelial ovarian cancer cell lines, inducing apoptosis and G2/M cell cycle arrest. In vivo experiments using orthotopic and patient-derived xenograft models showed significant tumor growth inhibition without apparent toxicity to vital organs. Unlike paclitaxel, BNZ-111 proved effective in paclitaxel-resistant cells, potentially by bypassing interaction with MDR1 and modulating β-3 tubulin expression to suppress microtubule dynamics., Conclusion: BNZ-111, with favorable drug-like properties, holds promise as a therapeutic option for platinum-resistant ovarian cancer, addressing a critical clinical need in gynecologic oncology., 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. The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

In genetic studies of cerebrovascular diseases, the optimal vessels to use as controls remain unclear. Our goal is to compare the transcriptomic profiles among 3 different types of control vessels: superficial temporal artery (STA), middle cerebral arteries (MCA), and arteries from the circle of Willis obtained from autopsies (AU). We examined the transcriptomic profiles of STA, MCA, and AU using RNAseq. We also investigated the effects of using these control groups on the results of the comparisons between aneurysms and the control arteries. Our study showed that when comparing pathological cerebral arteries to control groups, all control groups presented similar responses in the activation of immunological processes, the regulation of intracellular signaling pathways, and extracellular matrix productions, despite their intrinsic biological differences. When compared to STA, AU exhibited upregulation of stress and apoptosis genes, whereas MCA showed upregulation of genes associated with tRNA/rRNA processing. Moreover, our results suggest that the matched case-control study design, which involves control STA samples collected from the same subjects of matched aneurysm samples in our study, can improve the identification of non-inherited disease-associated genes. Given the challenges associated with obtaining fresh intracranial arteries from healthy individuals, our study suggests that using MCA, AU, or paired STA samples as controls are feasible strategies for future large-scale studies investigating cerebral vasculopathies. However, the intrinsic differences of each type of control should be taken into consideration when interpreting the results. With the limitations of each control type, it may be most optimal to use multiple tissues as controls., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Chemoresistant-epithelial ovarian cancer (EOC) has a poor prognosis, prompting the search for new therapeutic drugs. The diphenylbutylpiperidine (DPBP) class of antipsychotic drugs used in schizophrenia has shown anticancer effects. This study aimed to investigate the preclinical efficacy of penfluridol, fluspirilene, and pimozide (DPBP) using in vitro and in vivo models of EOC., Methods: Human EOC cell lines A2780, HeyA8, SKOV3ip1, A2780-CP20, HeyA8-MDR, and SKOV3-TR were treated with penfluridol, fluspirilene, and pimozide, and cell proliferation, apoptosis, and migration were assessed. The preclinical efficacy of DPBP was also investigated using in vivo mouse models, including cell lines and patient-derived xenografts (PDX) of EOC., Results: DPBP drugs significantly decreased cell proliferation in chemosensitive (A2780, HeyA8, and SKOV3ip1) and chemoresistant (A2780-CP20, HeyA8-MDR, and SKOV3-TR) cell lines. Among these drugs, penfluridol exerted a relatively stronger cytotoxic effect on all cell lines. Penfluridol significantly increased apoptosis and inhibited migration of EOC cells. In the cell line xenograft mouse model with HeyA8, the penfluridol group showed significantly decreased tumor weight compared with the control group. In the paclitaxel-resistant model with HeyA8-MDR, the penfluridol group had significantly decreased tumor weight compared with the paclitaxel or control groups. Penfluridol exerted anticancer effects on the PDX model., Conclusion: Penfluridol exerted significant anticancer effects on EOC cells and xenograft models, including PDX. Thus, penfluridol therapy, as a drug repurposing strategy, might be a potential therapeutic for EOCs., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2025. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Gene therapy using a protein-based CRISPR system in the brain has practical limitations due to current delivery systems, especially in the presence of arterial occlusion. To overcome these obstacles and improve stability, we designed a system for intranasal administration of gene therapy for the treatment of ischemic stroke. Methods: Nanoparticles containing the protein-based CRISPR/dCas9 system targeting Sirt1 were delivered intranasally to the brain in a mouse model of ischemic stroke. The CRISPR/dCas9 system was encapsulated with calcium phosphate (CaP) nanoparticles to prevent them from being degraded. They were then conjugated with β-hydroxybutyrates (bHb) to target monocarboxylic acid transporter 1 (MCT1) in nasal epithelial cells to facilitate their transfer into the brain. Results: Human nasal epithelial cells were shown to uptake and transfer nanoparticles to human brain endothelial cells with high efficiency in vitro . The intranasal administration of the dCas9/CaP/PEI-PEG-bHb nanoparticles in mice effectively upregulated the target gene, Sirt1 , in the brain, decreased cerebral edema and increased survival after permanent middle cerebral artery occlusion. Additionally, we observed no significant in vivo toxicity associated with intranasal administration of the nanoparticles, highlighting the safety of this approach. Conclusion: This study demonstrates that the proposed protein-based CRISPR-dCas9 system targeting neuroprotective genes in general, and SIRT1 in particular, can be a potential novel therapy for acute ischemic stroke., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Chronic hepatitis B virus (HBV) infection affects around 250 million people worldwide, causing approximately 887,000 deaths annually, primarily owing to cirrhosis and hepatocellular carcinoma (HCC). The current approved treatments for chronic HBV infection, such as interferon and nucleos(t)ide analogs, have certain limitations as they cannot completely eradicate covalently closed circular DNA (cccDNA). Considering that HBV replication relies on host transcription factors, focusing on host factors in the HBV genome may provide insights into new therapeutic targets against HBV. Therefore, understanding the mechanisms underlying viral persistence and hepatocyte pathogenesis, along with the associated host factors, is crucial. In this study, we investigated novel therapeutic targets for HBV infection by identifying gene and pathway networks involved in HBV replication in primary human hepatocytes (PHHs). Importantly, our study utilized cultured primary hepatocytes, allowing transcriptomic profiling in a biologically relevant context and enabling the investigation of early HBV-mediated effects., Methods: PHHs were infected with HBV virion particles derived from HepAD38 cells at 80 HBV genome equivalents per cell (Geq/cell). For transcriptomic sequencing, PHHs were harvested 1, 2-, 3-, 5-, and 7 days post-infection (dpi). After preparing the libraries, clustering and sequencing were conducted to generate RNA-sequencing data. This data was processed using Bioinformatics tools and software to analyze DEGs and obtain statistically significant results. Furthermore, qRT-PCR was performed to validate the RNA-sequencing results, ensuring consistent findings., Results: We observed significant alterations in the expression patterns of 149 genes from days 1 to 7 following HBV infection (R 2  > 0.7, q < 0.05). Functional analysis of these genes identified RNA-binding proteins involved in mRNA metabolism and the regulation of alternative splicing during HBV infection. Results from qRT-PCR experiments and the analysis of two validation datasets suggest that RBM14 and RPL28 may serve as potential biomarkers for HBV-associated HCC., Conclusions: Transcriptome analysis of gene expression changes during HBV infection in PHHs provided valuable insights into chronic HBV infection. Additionally, understanding the functional involvement of host factor networks in the molecular mechanisms of HBV replication and transcription may facilitate the development of novel strategies for HBV treatment., (© 2024. The Author(s).)

We report the synthesis and characterization of novel antimony(III) complexes: Sb(mpa) 3 ( 1 ), Sb(mmpa) 3 ( 2 ), Sb(mdpa) 3 ( 3 ), Sb(epa) 3 ( 4 ), Sb(empa) 3 ( 5 ), and Sb(edpa) 3 ( 6 ) (mpa = N -methoxypropanamide, mmpa = N -methoxy-2-methyl-propanamide, mdpa = N -methoxy-2,2-dimethylpropanamide, epa = N -ethoxypropanamide, empa = N -ethoxy-2-methylpropanamide, and edpa = N -ethoxy-2,2-dimethylpropanamide, via a salt-elimination reaction with SbCl 3 and sodium-substituted carboxamide. The molecular structure of 6 revealed the formation of a homoleptic conformer with a highly distorted pentagonal bipyramidal geometry, as determined by X-ray crystallography. Thermogravimetric analysis showed excellent volatility at elevated temperatures, with complex 4 displaying the lowest residual mass of 0.16% at 500 °C. For complexes 4 , 5 , and 6 , the temperature at a vapor pressure of 1 Torr and the enthalpy of vaporization were estimated to be 58, 64, and 45 °C and 83.31, 103.58, and 99.93 kJ/mol, respectively., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Magnesium, calcium, and barium heteroleptic complexes were synthesized by the substitution reaction of the bis(trimethylsilyl)amide of Mg(btsa) 2 ·DME, Ca(btsa) 2 ·DME, and Ba(btsa) 2 ·2DME with an ethereal group and hfac ligands (btsa = bis(trimethylsilyl)amide, DME = dimethoxyethane). The compounds Mg(dts)(hfac) 2 ( 1 ), Ca(dts)(hfac) 2 ( 2 ), Mg(dmts)(hfac) 2 ( 3 ), Ca(dmts)(hfac) 2 ( 4 ), and Ba(dmts)(hfac) 2 ( 5 ) were fabricated and analyzed using various techniques, including Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, thermogravimetric analyses, and elemental analysis (dts = 2,2-dimethyl-3,6,9-trioxa-2-siladecane, dmts = 2,2-dimethyl-3,6,9,12-tetraoxa-2-silatridecane, hfac = hexafluoroacetylacetonate). The structures of complexes 2, 4 , and 5 were confirmed using single-crystal X-ray crystallography; all complexes display monomeric structures. All compounds underwent trimethylsilylation of the coordinating ethereal alcohols (meeH and tmgeH) in the presence of HMDS as byproducts because of their increasing acidity originating from the electron-withdrawing hfac ligands. (meeH = 2-(2-methoxyethoxy)ethan-1-ol, tmgeH = tri(ethylene glycol) monoethyl ether, HMDS = hexamethyldisilazane)., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

We analysed the skulls and faces of Korean subjects using anthropometric methods to understand the anatomical characteristics of the eyeball and eye orbit region of Korean population and to determine the correlations between the hard and soft tissues around the eyeball and eye orbit region. In total, 82 sections in the region were measured to determine the correlations; among them, 34 showed significant differences by sex, and 6 showed significant differences by age. As the distance from the centre of the eye lens to the eye orbit is calculated as a ratio, we determined that the centre of the eye lens is located relatively on the lateral and superior position in each eye orbit in front view. Fourteen sections that could be used for craniofacial reconstruction/approximation in men and women were selected. Regression equations were derived according to the correlation of each section, and their reliabilities were verified by out of sample validation tests. Therefore, our results increase the accuracy of eyeball position determination, which would be useful for more efficient craniofacial reconstruction/approximation of the Korean population and should improve the efficiency of facial recognition., (© 2024. The Author(s).)

This study uses annular circular rings to create multi-band applications using crescent-shaped patch antennas. It is designed to be made up of five circular, annular rings nested inside of each other. Three annular rings are positioned and merged on top of the larger rings, with two annular rings set along the bottom of the feed line. The factors that set them apart, such as bandwidths, radiation patterns, gain, impedance, and return loss (RL), are analysed. The outcomes show how compact the multi-band annular ring antenna is. The proposed circular annular ring antenna has return losses of -33 dB and operates at two frequencies: 3.1 GHz and 9.3 GHz. This design is modelled and simulated using ANSYS HFSS. The outcomes of the simulation and the tests agree quite well. The X band and WLAN resonant bands have bandwidth capacities of 500 and 4300 MHz, respectively. Additionally, the circular annular ring antenna design is advantageous for most services at these operating bands.

Cell-based tissue engineering often requires the use of scaffolds to provide a three-dimensional (3D) framework for cell proliferation and tissue formation. Polycaprolactone (PCL), a type of polymer, has good printability, favorable surface modifiability, adaptability, and biodegradability. However, its large-scale applicability is hindered by its hydrophobic nature, which affects biological properties. Composite materials can be created by adding bioactive materials to the polymer to improve the properties of PCL scaffolds. Osteolectin is an odontogenic factor that promotes the maintenance of the adult skeleton by promoting the differentiation of LepR+ cells into osteoblasts. Therefore, the aim of this study was to evaluate whether 3D-printed PCL/osteolectin scaffolds supply a suitable microenvironment for the odontogenic differentiation of human dental pulp cells (hDPCs). The hDPCs were cultured on 3D-printed PCL scaffolds with or without pores. Cell attachment and cell proliferation were evaluated using EZ-Cytox. The odontogenic differentiation of hDPCs was evaluated by alizarin red S staining and alkaline phosphatase assays. Western blot was used to evaluate the expression of the proteins DSPP and DMP-Results: The attachment of hDPCs to PCL scaffolds with pores was significantly higher than to PCL scaffolds without pores. The odontogenic differentiation of hDPCs was induced more in PCL/osteolectin scaffolds than in PCL scaffolds, but there was no statistically significant difference. 3D-printed PCL scaffolds with pores are suitable for the growth of hDPCs, and the PCL/osteolectin scaffolds can provide a more favorable microenvironment for the odontogenic differentiation of hDPCs., (© 2024 IOP Publishing Ltd.)

Background: In breast surgery, achieving esthetic outcomes with symmetry is crucial. The nipple-areolar complex (NAC) plays a significant role in breast characteristic measurement. Various technologies have advanced measurement techniques, and light detection and ranging (LiDAR) technology using three-dimensional scanning has been introduced in engineering. Increasing effort has been exerted to integrate such technologies into the medical field. This study focused on measuring NAC using a LiDAR camera, comparing it with traditional methods, and aimed to establish the clinical utility of LiDAR for obtaining favorable esthetic results., Methods: A total of 44 patients, who underwent breast reconstruction surgery, and 65 NACs were enrolled. Measurements were taken (areolar width [AW], nipple width [NW] and nipple projection [NP]) using traditional methods (ruler and photometry) and LiDAR camera. To assess correlations and explore clinical implications, patient demographics and measurement values were collected., Results: NAC measurements using a periscope and LiDAR methods were compared and correlated. LiDAR measurement accuracy was found to be high, with values above 95% for AW, NW and NP. Significant positive correlations were observed between measurements obtained through both methods for all parameters. When comparing body mass index, breast volume with AW and NW with NP, significant correlations were observed. These findings demonstrate the reliability and utility of LiDAR-based measurements in NAC profile assessment and provide valuable insights into the relationship between patient demographics and NAC parameters., Conclusions: LiDAR-based measurements are effective and can replace classical methods in NAC anthropometry, contributing to consistent and favorable esthetic outcomes in breast surgery., Level of Evidence Ii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266 ., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

De novo drug design aims to rationally discover novel and potent compounds while reducing experimental costs during the drug development stage. Despite the numerous generative models that have been developed, few successful cases of drug design utilizing generative models have been reported. One of the most common challenges is designing compounds that are not synthesizable or realistic. Therefore, methods capable of accurately assessing the chemical structures proposed by generative models for drug design are needed. In this study, we present AnoChem, a computational framework based on deep learning designed to assess the likelihood of a generated molecule being real. AnoChem achieves an area under the receiver operating characteristic curve score of 0.900 for distinguishing between real and generated molecules. We utilized AnoChem to evaluate and compare the performances of several generative models, using other metrics, namely SAscore and Fréschet ChemNet distance (FCD). AnoChem demonstrates a strong correlation with these metrics, validating its effectiveness as a reliable tool for assessing generative models. The source code for AnoChem is available at https://github.com/CSB-L/AnoChem., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.)

Arteriovenous malformations (AVMs) are congenital vascular anomalies with a poor prognosis. AVMs are considered intractable diseases, as there is no established approach for early diagnosis and treatment. Therefore, this study aimed to provide new evidence by analyzing microRNAs (miRNAs) associated with AVM. We present fundamental evidence for the early diagnosis and treatment of AVM by analyzing miRNAs in the endothelial cells of AVMs. This study performed sequencing and validation of miRNAs in endothelial cells from normal and AVM tissues. Five upregulated and two downregulated miRNAs were subsequently analyzed under hypoxia and vascular endothelial growth factor (VEGF) treatment by one-way analysis of variance (ANOVA). Under hypoxic conditions, miR-135b-5p was significantly upregulated in the AVM compared to that under normal conditions, corresponding to increased endothelial activity ( p -value = 0.0238). VEGF treatment showed no significant increase in miR-135b-5p under normal conditions, however, a surge in AVM was observed. Under both hypoxia and VEGF treatment, comparison indicated a downregulation of miR-135b-5p in AVM. Therefore, miR-135b-5p was assumed to affect the pathophysiological process of AVM and might play a vital role as a potential biomarker of AVMs for application related to diagnosis and treatment.

Polycyclic aromatic hydrocarbons (PAHs) are widespread pollutants associated with several adverse health effects and PAH-induced oxidative stress has been proposed as a potential mechanism. This study evaluated the associations of single and multiple PAHs exposure with oxidative stress within the Korean adult population, using serum gamma glutamyltransferase (GGT) as an oxidative stress marker. Data from the Second Korean National Environmental Health Survey (2012-2014) were analyzed. For analysis, 5225 individuals were included. PAH exposure was assessed with four urinary PAH metabolites: 1-hydroxyphenanthrene, 1-hydroxypyrene, 2-hydroxyfluorene, and 2-naphthol. After adjusting for age, sex, body mass index, drinking, passive smoking, and current smoking (model 1), as well as the presence of diabetes and hepatobiliary diseases (model 2), complex samples general linear model regression analyses for each metabolite revealed a significant positive association between Ln(1-hydroxyphenanthrene) and Ln(GGT) (model 1: β = 0.040, p < 0.01 and model 2: β = 0.044, p < 0.05). For the complete dataset (n = 4378), a significant positive association was observed between mixture of four urinary PAH metabolites and serum GGT in both the quantile g-computation and the Bayesian kernel machine regression analysis. Our study provides evidence for the association between mixed PAH exposure and oxidative stress., (© 2024. The Author(s).)

Background/aim: Fat grafting has been widely used for soft-tissue augmentation. External volume expansion (EVE) is a favorable tool for improvement in the rate of fat graft retention. However, few studies have focused on the most appropriate time for its implementation. In this study, BALB/c nude mice were used to investigate the effective time for the implementation of external volume expansion to improve the rate of fat retention., Materials and Methods: Sixteen mice were divided into four groups, and EVE was performed at different time points before or both before and after fat grafting. Fat tissue from a human donor was injected into the mice following EVE. Visual assessment, micro-computed tomography analysis, and histopathological evaluation were used to assess fat retention., Results: After 10 weeks, the group that underwent EVE 5 days before fat grafting demonstrated a significantly higher preserved fat volume, as determined by micro-computed tomography (p<0.05). Moreover, the group that received additional EVE after fat grafting exhibited a higher retention rate compared to the groups receiving EVE only before grafting (p<0.05). Histopathological analysis indicated that swelling, edema, and inflammation were more pronounced in the group with EVE immediately before grafting, while angiogenesis and lipogenesis were more active in the group with additional EVE after grafting., Conclusion: EVE is a safe and effective approach for improving the rate of fat graft retentions. Furthermore, the timing of external tissue expansion plays a crucial role in fat retention. Based on our animal study, performing EVE immediately before and after fat grafting may be an effective strategy for enhancing the rate of fat graft retentions., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Postoperative scar formation is inevitable, and a gold standard management has not been established to date. Due to the fact long and large scar formation occurs in reconstructive surgery, this study analyzed the relationship between various factors in patients who received breast reconstruction using latissimus dorsi (LD) flap to investigate appropriate and effective management approaches., Patients and Methods: Twenty-seven patients who underwent breast reconstruction between June 2014 and January 2015 received laser therapy on their LD donor site at the Kyungpook National University Chilgok Hospital. Scar evaluation was performed on both the surgical scar and intact skin on the contralateral side. Scar evaluation was conducted at five specific points, 2 cm from the midpoint of the scar on each side. Laser treatment was performed at 4-week intervals, and patients were then followed-up for 6 months. To assess scars, gross images were taken using the same settings. In addition, spectrophotometry was used for color assessment, durometer for texture and pressure evaluation, and Vernier calipers and height gauges for a more precise and objective approach., Results: The mean age of the participants was 45.7 years, and the mean body mass index was 22.1 kg/m 2 The operator-evaluated scar scale scores were 107.2 and 97.3 in the experimental and control groups, respectively. In the patient-rated questionnaire, the scores were 62.3 and 59.4 in the experimental and control groups, respectively., Conclusion: When analyzing early-stage postoperative scars based on various factors, laser therapy is considered a very useful scar management approach. Additionally, when performing reconstructive surgery, tension force is regarded as a significant factor to take into account since it affects scar widening., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: To investigate the effects of helmet therapy on plagiocephaly, according to head circumference, cephalic index (CI), and skull height. Plagiocephaly is a condition in which the skull is congenitally asymmetrical or affected by acquired factors such as compression in the womb or the habit of sleeping on one side. Although there are numerous studies on the effectiveness of helmet therapy for plagiocephaly, research on its effectiveness on skull shape is lacking., Methods: We conducted a prospective study on 400 patients who underwent helmet therapy. The infants were enrolled and the therapy was explained to the caregiver when the child had positional plagiocephaly and had a cranial vault asymmetry (CVA) exceeding 10 mm or a CVA index (CVAI) exceeding 3.5%. The CVA and CVAI changes were compared to investigate the effectiveness of helmet therapy according to head circumference, CI, and skull height., Results: A significant treatment effect was observed for CI values between 90 and 103. The treatment effect was found to increase with greater skull height. However, no significant difference was observed in the effectiveness of helmet therapy according to head circumference., Conclusions: According to the findings, the effectiveness of helmet therapy in children with positional plagiocephaly is greater for children with higher skulls and for those with CI values between 90 and 103; it is unrelated to head circumference. Based on these results, we can provide predictions of the effectiveness of helmet therapy to caregivers of children with positional plagiocephaly., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Background: Coronary artery bypass graft (CABG) is generally used to treat complex coronary artery disease. Treatment success is affected by neointimal hyperplasia (NIH) of graft and anastomotic sites. Although sirolimus and rosuvastatin individually inhibit NIH progression, the efficacy of combination treatment remains unknown., Methods: We identified cross-targets associated with CABG, sirolimus, and rosuvastatin by using databases including DisGeNET and GeneCards. GO and KEGG pathway enrichment analyses were conducted using R studio, and target proteins were mapped in PPI networks using Metascape and Cytoscape. For in vivo validation, we established a balloon-injured rabbit model by inducing NIH and applied a localized perivascular drug delivery device containing sirolimus and rosuvastatin. The outcomes were evaluated at 1, 2, and 4 weeks post-surgery., Results: We identified 115 shared targets between sirolimus and CABG among databases, 23 between rosuvastatin and CABG, and 96 among all three. TNF, AKT1, and MMP9 were identified as shared targets. Network pharmacology predicted the stages of NIH progression and the corresponding signaling pathways linked to sirolimus (acute stage, IL6/STAT3 signaling) and rosuvastatin (chronic stage, Akt/MMP9 signaling). In vivo experiments demonstrated that the combination of sirolimus and rosuvastatin significantly suppressed NIH progression. This combination treatment also markedly decreased the expression of inflammation and Akt signaling pathway-related proteins, which was consistent with the predictions from network pharmacology analysis., Conclusions: Sirolimus and rosuvastatin inhibited pro-inflammatory cytokine production during the acute stage and regulated Akt/mTOR/NF-κB/STAT3 signaling in the chronic stage of NIH progression. These potential synergistic mechanisms may optimize treatment strategies to improve long-term patency after CABG., (© 2024. The Author(s).)

Gallic acid (GA), a phenolic compound naturally found in many plants, exhibits potential preventive and therapeutic roles. However, the underlying molecular mechanisms of its diverse biological activities remain unclear. Here, we investigated possible mechanisms of GA function through a transcriptome-based analysis using LINCS L1000, a publicly available data resource. We compared the changes in the gene expression profiles induced by GA with those induced by FDA-approved drugs in three cancer cell lines (A549, PC3, and MCF7). The top 10 drugs exhibiting high similarity with GA in their expression patterns were identified by calculating the connectivity score in the three cell lines. We specified the known target proteins of these drugs, which could be potential targets of GA, and identified 19 potential targets. Next, we retrieved evidence in the literature that GA likely binds directly to DNA polymerase β and ribonucleoside-diphosphate reductase. Although our results align with previous studies suggesting a direct and/or indirect connection between GA and the target proteins, further experimental investigations are required to fully understand the exact molecular mechanisms of GA. Our study provides insights into the therapeutic mechanisms of GA, introducing a new approach to characterizing therapeutic natural compounds using transcriptome-based analyses.

Background: Lymphovenous anastomosis (LVA) enables lymphatic fluid to drain into the venous system. However, no study has investigated the association between LVA and heart failure (HF) caused by fluid overload in the blood circulating system. The purpose of our study was to determine whether LVA increases the risk of HF and mortality., Material and Methods: This nationwide retrospective study evaluated a total of 1400 lymphedema patients who underwent LVA and two control cohorts with 28 000 lymphedema who did not undergo LVA and 70 000 age-matched and sex-matched participants from the Korean National Health Insurance database were included. Blood pressure, body mass index (BMI), glucose and cholesterol levels, smoking history, and comorbidities were obtained during National Health Insurance Service - Health Screening (NHIS-HealS). The incidence, adjusted risk for HF, and mortality were evaluated., Results: Adjusted HRs for HF were 1.20 (confidence interval [CI], 1.03-1.40) and 1.30 (CI, 1.12-1.50), referenced by the general population control cohort and patients with lymphedema without LVA, respectively. In age, sex, BMI, and smoking status-stratified analyses, heightened risk of HF was evident across all sexes, spanning both young and old age groups, encompassing individuals with various smoking statuses, and those with a BMI of 18.5 or higher. Among these groups, the risk was notably greater in males compared to females, higher in younger individuals as opposed to older ones, and further elevated within the BMI range of 18.5-25., Conclusions: LVA is associated with an increased HF risk, independent of cardiovascular risk factors and associated comorbidities. This association is prominent in participants aged <50 years, in males, and in the normal-to-obese (BMI ≥18.5 kg/m 2 ) group. Among patients with lymphedema, LVA did not significantly affect mortality., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

A reformed particle swarm optimization (R PSO )-based up-conversion mixer circuit is proposed for radar application in this paper. In practice, a non-optimized up-conversion mixer suffers from high power consumption, poor linearity, and conversion gain. Therefore, the R PSO algorithm is proposed to optimize the up-conversion mixer. The novelty of the proposed R PSO algorithm is it helps to solve the problem of local optima and premature convergence in traditional particle swarm optimization (T PSO ). Furthermore, in the R PSO , a velocity position-based convergence (VP C ) and wavelet mutation (W M ) strategy are used to enhance R PSO 's swarm diversity. Moreover, this work also features novel circuit configurations based on the two-fold transconductance path (T TP ), a technique used to improve linearity. A differential common source (D CS ) amplifier is included in the primary transconductance path (P TP ) of the T TP . As for the subsidiary transconductance path (S TP ), the enhanced cross-quad transconductor (E CQT ) is implemented within the T TP . A benchmark function verification is conducted to demonstrate the effectiveness of the R PSO algorithm. The proposed R PSO has also been compared with other optimization algorithms such as the genetic algorithm (GA) and the non-dominated sorting genetic algorithm II (NSGA-II). By using R PSO , the proposed optimized mixer achieves a conversion gain (CG) of 2.5 dB (measured). In this study, the proposed mixer achieves a 1 dB compression point (OP 1 dB) of 4.2 dBm with a high linearity. In the proposed mixer, the noise figure (NF) is approximately 3.1 dB. While the power dissipation of the optimized mixer is 3.24 mW. Additionally, the average time for R PSO to design an up-conversion mixer is 4.535 s. Simulation and measured results demonstrate the excellent performance of the R PSO optimized up-conversion mixer.

Background: The FGF/FGFR signaling pathway plays a critical role in human cancers. We analyzed the anti-tumor effect of AZD4547, an inhibitor targeting the FGF/FGFR pathway, in epithelial ovarian cancer (EOC) and strategies on overcoming AZD4547 resistance., Methods: The effect of AZD4547 on cell viability/migration was evaluated and in vivo experiments in intraperitoneal xenografts using EOC cells and a patient-derived xenograft (PDX) model were performed. The effect of the combination of AZD4547 with SU11274, a c-Met-specific inhibitor, FGF19-specific siRNA, or an FGFR4 inhibitor was evaluated by MTT assay., Results: AZD4547 significantly decreased cell survival and migration in drug-sensitive EOC cells but not drug-resistant cells. AZD4547 significantly decreased tumor weight in xenograft models of drug-sensitive A2780 and SKOV3ip1 cells and in a PDX with drug sensitivity but not in models with drug-resistant A2780-CP20 and SKOV3-TR cells. Furthermore, c-Met expression was high in SKOV3-TR and HeyA8-MDR cells, and co-administration of SU11274 and AZD4547 synergistically induced cell death. In addition, expressions of FGF19 and FGFR4 were high in A2780-CP20 cells. Combining AZD4547 with FGF19 siRNA or with a selective FGFR4 inhibitor led to significantly reduced cell proliferation in A2780-CP20 cells., Conclusions: This study showed that AZD4547 has significant anti-cancer effects in drug-sensitive cells and PDX models but not in drug-resistant EOC cells. In drug-resistant cells, the expression level of c-Met or FGF19/FGFR4 may be a predictive biomarker for AZD4547 treatment response, and a combination strategy of drugs targeting c-Met or FGF19/FGFR4 together with AZD4547 may be an effective therapeutic strategy for EOC., (© 2024. The Author(s).)

In this article, we discuss the synthesis of eight novel zirconium and hafnium complexes containing amidoxime ligands as potential precursors for atomic layer deposition (ALD). Two amidoximes, viz., ( E )- N '-hydroxy- N , N -dimethylacetimidamide (mdaoH) and ( Z )- N '-hydroxy- N , N -dimethylpivalimidamide (tdaoH), along with their Zr and Hf homoleptic complexes, Zr(mdao) 4 ( 1 ), Hf(mdao) 4 ( 2 ), Zr(tdao) 4 ( 3 ), and Hf(tdao) 4 ( 4 ) were prepared. We further synthesized heteroleptic compounds with different physical properties by introducing cyclopentadienyl (Cp) ligand, namely, CpZr(mdao) 3 ( 5 ), CpHf(mdao) 3 ( 6 ), CpZr(tdao) 3 ( 7 ), and CpHf(tdao) 3 ( 8 ). Thermogravimetric analysis was used for the assessment of the evaporation characteristics of complexes 1 , 2 , 5 , and 6 , and it revealed multistep weight losses with high residues. On the other hand, the thermogravimetric analysis curves of complexes 3 , 4 , 7 , and 8 comprising tdao ligands revealed single-step weight losses with moderate residues. Single-crystal X-ray diffraction studies of complexes 1 , 3 , and 7 showed that all of the complexes have monomeric molecular structures. Complex 7 exhibited a low melting point (75 °C), good volatility, and high thermal stability compared with other complexes. Therefore, an atomic layer deposition process for the growth of ZrO 2 was developed by using ZrCp(tdao) 3 ( 7 ) as a novel precursor.

Life-threatening airway obstruction is a major concern in patients with Pierre-Robin sequence. Tongue-lip adhesion (TLA) has been used to manage airway obstruction. The authors present the case of a female neonate with Pierre-Robin sequence who presented with airway obstruction and a cleft palate. She underwent a TLA procedure with modified tongue base suspension (TBS). Endoscopy was used to check and control the traction of the tongue base to enable unobstructed self-ventilation. Positive outcomes including improved O2 saturation and weight gain were noted. The effectiveness of TLA was enhanced by using TBS with real-time endoscopy to evaluate the oropharyngeal airway space required to alleviate airway obstruction. The use of endoscopy enabled us to check and determine how much the tongue base should be tracted by manipulating the tongue anteriorly and posteriorly. The authors report transoral endoscopy-assisted TLA and modified TBS., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

The proliferation of radar technology has given rise to a growing demand for advanced, high-performance transmitter front-ends operating in the 24 GHz frequency band. This paper presents a design analysis of a radio frequency (RF) transmitter (TX) front-end operated at a 24 GHz frequency and designed using 65 nm complementary metal-oxide-semiconductor (CMOS) technology for radar applications. The proposed TX front-end design includes the integration of an up-conversion mixer and power amplifier (PA). The up-conversion mixer is a Gilbert cell-based design that translates the 2.4 GHz intermediate frequency (IF) signal and 21.6 GHz local oscillator (LO) signal to the 24 GHz RF output signal. The mixer is designed with a novel technique that includes a duplex transconductance path (D TP ) for enhancing the mixer's linearity. The D TP of the mixer includes a primary transconductance path (P TP ) and a secondary transconductance path (S TP ). The P TP incorporates a common source (CS) amplifier, while the S TP incorporates an improved cross-quad transconductor (I CQT ). The integrated PA in the TX front-end is a class AB tunable two-stage PA that can be tuned with the help of varactors as a synchronous mode to increase the PA bandwidth or stagger mode to obtain a high gain. The PA is tuned to 24 GHz as a synchronous mode PA for the TX front-end operation. The proposed TX front-end showed an excellent output power of 11.7 dBm and dissipated 7.5 mW from a 1.2 V supply. In addition, the TX front-end achieved a power-added efficiency (PAE) of 47% and 1 dB compression point (OP 1 dB) of 10.5 dBm. In this case, the output power is 10.5 dBm higher than the linear portion of the response. The methodologies presented herein have the potential to advance the state of the art in 24 GHz radar technology, fostering innovations in fields such as autonomous vehicles, industrial automation, and remote sensing.

Intimal hyperplasia (IH) is a major cause of vascular restenosis after bypass surgery, which progresses as a series of processes from the acute to chronic stage in response to endothelial damage during bypass grafting. A strategic localized drug delivery system that reflects the pathophysiology of IH and minimizes systemic side effects is necessary. In this study, the sequential release of sirolimus, a mechanistic target of rapamycin (mTOR) inhibitor, and statin, an HMG-COA inhibitor, was realized as a silk fibroin-based microneedle device in vivo. The released sirolimus in the acute stage reduced neointima (NI) and vascular fibrosis through mTOR inhibition. Furthermore, rosuvastatin, which was continuously released from the acute to chronic stage, reduced vascular stiffness and apoptosis through the inactivation of Yes-associated protein (YAP). The sequential release of sirolimus and rosuvastatin confirmed the synergistic treatment effects on vascular inflammation, VSMC proliferation, and ECM degradation remodeling through the inhibition of transforming growth factor (TGF)-beta/NF-κB pathway. These results demonstrate the therapeutic effect on preventing restenosis with sufficient vascular elasticity and significantly reduced IH in response to endothelial damage. Therefore, this study suggests a promising strategy for treating coronary artery disease through localized drug delivery of customized drug combinations., Competing Interests: Declaration of Competing Interest The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Ulipristal acetate (UPA) is a selective progesterone receptor modulator and is used for the treatment of uterine leiomyoma (a benign tumor). Uterine sarcoma which is highly malignant cancer with a poor prognosis is clinically resembled with uterine leiomyoma. There has been no experimental research on the effect of UPA on uterine sarcoma. In this study, we examined the efficacy of UPA in uterine sarcoma with in vitro and in vivo animal models. Cytotoxicity of UPA was determined in uterine sarcoma cell lines (MES-SA, SK-UT-1, and SK-LMS-1). Apoptotic genes and signaling pathways affected by UPA were analyzed by complementary DNA (cDNA) microarray of uterine sarcoma cell lines and western blot, respectively. An in vivo efficacy of UPA was examined with uterine sarcoma cell line- and patient-derived xenograft (PDX) mice models. UPA inhibited cell growth in uterine sarcoma cell lines and primary culture cells from a PDX mouse (PDX-C). cDNA microarray analysis revealed that CCL2 was highly down-regulated by UPA. Phosphorylation and the total expression of STAT3 were inhibited by UPA. UPA also inhibited CCL2 and STAT3 in PDX-C. The inhibitory effect of UPA had not changed in the overexpression of PR and treatment of progesterone. In vivo efficacy studies with cell line-derived xenografts and a PDX model with leiomyosarcoma, a typical uterine sarcoma, demonstrated that UPA significantly decreased tumor growth. UPA had significant anti-tumor effects in uterine sarcoma through the inhibition of STAT3/CCL2 signaling pathway and might be a potential therapeutic agent to treat this disease., 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 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Frontal sinus anterior wall defects occur because of various diseases, causing not only aesthetic problems, such as forehead bulging and upper eyelid ptosis, but also exerting physical pressure on the brain or optic nerve. Therefore, this study aimed to evaluate the prognosis of performing split-rib bone graft for frontal sinus anterior wall defects., Methods: This study included 30 patients who received a split-rib bone graft for a frontal sinus anterior wall defect. The sizes and volumes of the defects and grafts were measured using three-dimensional computed tomography before, after, and every 6 months for 2 years after the surgery. The Medical Imaging Interaction Toolkit was used for analysis., Results: The average size and volume of the grafts were 27.29 cm 2 and 5.88 cm 3 , whereas they were 23.76 cm 2 and 4.80 cm 3 at 24 months after surgery, respectively. In a graft size and volume of less than 27 cm 2 and 6 cm 3 , respectively, the rate of graft take was greater than 80% during long-term observation. The younger the age, the higher the rate of graft take. No difference was found in the defect causes. Absorption occurred for up to 18 months., Conclusions: Frontal bone defect reconstruction revealed the stable results of the split-rib bone graft over a long period when the size and volume were less than 27 cm 2 and 6 cm 3 , respectively. Furthermore, bone resorption was seen in more than 20% to 30% of the patients, and the rate of resorption increased with age; thus, it is appropriate to consider overcorrection and other reconstruction methods., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2023 by the American Society of Plastic Surgeons.)

In metabolic engineering, predicting gene overexpression targets remains challenging because both endogenous and heterologous genes in a large metabolic space can be candidates, in contrast to gene knockout targets that are confined to endogenous genes. We report the development of iBridge that identifies positive and negative metabolites exerting positive and negative impacts on product formation, respectively, based on the sum of covariances of their outgoing (consuming) reaction fluxes for a target chemical. Then, "bridge" reactions converting negative metabolites to positive metabolites are identified as overexpression targets, while the opposites as downregulation targets. Using iBridge, overexpression and downregulation targets are suggested for the production of 298 chemicals and validated for 36 chemicals experimentally demonstrated in previous studies. Finally, iBridge is employed to engineer Escherichia coli strains capable of producing 10.3 g/L of D-panthenol, a compound not previously produced, as well as putrescine and 4-hydroxyphenyllactate at enhanced titers, 63.7 and 8.3 g/L, respectively., Competing Interests: Declaration of interests S.Y.L. and J.E.Y. declare that they have conflict of interest as the microbial production of 4-hydroxyphenyllactate has been filed as a patent (Korean patent application no. 10-2015-0067345) for potential commercialization. S.Y.L. is a member of the advisory board of Cell Systems., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This study describes the synthesis of 12 new germanium complexes containing β-diketonate and/or N -alkoxy carboxamidate-type ligands as precursors for GeO 2 through atomic layer deposition (ALD). A series of Ge(β-diketonate)Cl complexes such as Ge(acac)Cl ( 1 ) and Ge(tmhd)Cl ( 2 ) were synthesized by using acetylacetone (acacH) and 2,2,6,6-tetramethyl-3,5-heptanedione (tmhdH). N -Alkoxy carboxamidate-type ligands such as N -methoxypropanamide (mpaH), N -methoxy-2,2-dimethylpropanamide (mdpaH), N -ethoxy-2-methylpropanamide (empaH), N -ethoxy-2,2-dimethylpropanamide (edpaH), and N -methoxybenzamide (mbaH) were used to afford further substituted complexes Ge(acac)(mpa) ( 3 ), Ge(acac)(mdpa) ( 4 ), Ge(acac)(empa) ( 5 ), Ge(acac)(edpa) ( 6 ), Ge(acac)(mba) ( 7 ), Ge(tmhd)(mpa) ( 8 ), Ge(tmhd)(mdpa) ( 9 ), Ge(tmhd)(empa) ( 10 ), Ge(tmhd)(edpa) ( 11 ), and Ge(tmhd)(mba) ( 12 ), respectively. Thermogravimetric analysis curves, which mostly exhibited single-step weight losses, were used to determine the evaporation properties of complexes 1 - 12 . Interestingly, liquid complex 2 has no residue at 198 °C and therefore exhibits excellent vaporization properties and high volatility. Single-crystal X-ray diffraction studies of 1 and 7 demonstrated that the complexes had monomeric molecular structures with germanium chelated by the oxygen atoms of one or two bidentate ligands, respectively. An ALD process was developed for the growth of GeO 2 using Ge(tmhd)Cl ( 2 ) as a new precursor and H 2 O 2 as an oxidant. This study demonstrates the achievement of self-limiting growth of GeO 2 films by varying the duration of injection/purge, with an observed ALD window at deposition temperatures ranging from 300 to 350 °C. The saturated growth per cycle of the GeO 2 film was determined as 0.27 Å/cycle at a deposition temperature of 300 °C. The deposited films were observed to be amorphous consisting of GeO 2 ., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Competing Interests: The authors have nothing to disclose.

A sagittal fracture at the temporal root of the zygomatic arch (ZAR) often occurs as a component of zygomaticomaxillary complex (ZMC) fractures. However, this area is difficult to access, and anchorage is limited due to the unstable structure around it. Therefore, a preauricular approach using single-screw fixation is proposed, and this study reports its results and usefulness. Forty-four patients with sagittal fractures of ZAR occurring with ZMC fractures were evaluated from 2012 to 2021. Open reduction and internal fixation were performed on all patients with ZMC fractures. Closed reduction using Dingman incision and external finger pressure in group A (indirect approach; 30 patients) and single-screw fixation using a preauricular approach in group B (direct approach; 14 patients) were performed to address sagittal fractures in ZAR. For single-screw fixation, the additional mean operation time was 11.34±3.25 minutes. On postoperative 3-dimensional computed tomography and plain radiographs, group B showed more accurate reduction and less deformity and trismus ( P <0.05). Moreover, a normal diet was initiated more quickly in group B than in group A ( P <0.05). Some cases in group A showed nonunion or malunion. This study revealed that a direct approach (group B) toward sagittal fractures of ZAR is recommended due to more accurate results and fewer complications than those observed with the indirect approach (group A). Moreover, the total operation time and complications may be lesser than those with the bicoronal approach., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Background/aim: The tongue is an important anatomical structure, playing an significant role in natural speech, swallowing, and sense of taste. Immediate reconstruction using autologous tissue must be performed following glossectomy for tongue cancer to improve patient quality of life. This study aimed to demonstrate the usefulness of a surgical technique using the free vertical latissimus dorsi flap (FvLDF) for tongue reconstructions using autologous tissue., Patients and Methods: Among patients who underwent total glossectomy for tongue cancer from November 2014 to February 2023, we selected 10 patients who underwent immediate tongue reconstruction with a radial free forearm flap (RFFF) or free anterolateral thigh flap and four patients who underwent FvLDF. The patients were compared regarding postoperative function (width of oropharyngeal space in computed tomography, language-speech evaluation), aesthetic results, and features., Results: All four patients who underwent FvLDF showed successful flap survival, with no severe complications. Because vertical incision was made during flap harvest with primary closure possible with the mid-axillary line, donor morbidity was significantly lower in patients who underwent reconstruction with FvLDF than in those who underwent reconstruction with RFFF, and good aesthetic results were obtained. In comparing the oropharyngeal space of patients on neck CT preoperatively and postoperatively, the width increase rate of patients who underwent reconstruction with FvLDF was significantly smaller. FvLDF patients demonstrated good speech and swallowing functions., Conclusion: Considering the advantages of reconstruction with FvLDF in terms of features and aesthetic results, this surgical technique may be a reliable alternative technique for tongue defects after glossectomy., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Although mRNA delivery technology is very promising, problems in safety and transport arise due to the intrinsically low thermodynamic stability of the current mRNA carriers. Considering that mRNAs are filamentous and a nanotube is one of the most thermodynamically stable shapes among nanoassemblies, a nanotube is one of the most stable supramolecular structures that can be assembled with mRNA. Here, we develop a nanotube-shaped filamentous mRNA delivery platform that shows exceptionally high thermodynamic stability. The key to the development of the mRNA nanotube is the design of self-adjusting supramolecular building blocks (SABs) that have two disparate properties, i.e., dynamic property and stiffness, in a single molecule. The counterbalance of the dynamic property and stiffness in SABs enables the coating of mRNA by winding its way through the flexible and irregular mRNA chain via cooperative interactions. SAB nanotubes with targeting ligands installed show a high uptake efficiency in mammalian cells and controllable gene expression behavior. Thus, the mRNA nanotube provides an enabling technology toward the development of safe and stable mRNA vaccines and therapeutics.

Novel Sn precursors, Sn(tbip) 2 , Sn(tbtp) 2 , and Sn(tbta) 2 , were synthesized and characterized using various analytical techniques and density functional theory calculations. These precursors contained cyclic amine ligands derived from iminopyrrolidine. X-ray crystallography revealed the formation of monomeric SnL 2 with distorted seesaw geometry. Thermogravimetric analysis demonstrated the exceptional volatility of all complexes. Sn(tbtp) 2 showed the lowest residual weight of 2.7% at 265 °C. Sn 3 N 4 thin films were successfully synthesized using Sn(tbtp) 2 as the Sn precursor and NH 3 plasma. The precursor exhibited ideal characteristics for atomic layer deposition, with a saturated growth per cycle value of 1.9 Å cy -1 and no need for incubation when the film was deposited at 150-225 °C. The indirect optical bandgap of the Sn 3 N 4 film was approximately 1-1.2 eV, as determined through ultraviolet-visible spectroscopy. Therefore, this study suggests that the Sn 3 N 4 thin films prepared using the newly synthesized Sn precursor are suitable for application in thin-film photovoltaic devices.

Hyponatremia is primarily a water balance disorder associated with high morbidity and mortality. The pathophysiological mechanisms behind hyponatremia are multifactorial, and diagnosing and treating this disorder remains challenging. In this review, the classification, pathogenesis, and step-by-step management approaches for hyponatremia in patients with liver disease are described based on recent evidence. We summarize the five sequential steps of the traditional diagnostic approach: 1) confirm true hypotonic hyponatremia, 2) assess the severity of hyponatremia symptoms, 3) measure urine osmolality, 4) classify hyponatremia based on the urine sodium concentration and extracellular fluid status, and 5) rule out any coexisting endocrine disorder and renal failure. Distinct treatment strategies for hyponatremia in liver disease should be applied according to the symptoms, duration, and etiology of disease. Symptomatic hyponatremia requires immediate correction with 3% saline. Asymptomatic chronic hyponatremia in liver disease is prevalent and treatment plans should be individualized based on diagnosis. Treatment options for correcting hyponatremia in advanced liver disease may include water restriction; hypokalemia correction; and administration of vasopressin antagonists, albumin, and 3% saline. Safety concerns for patients with liver disease include a higher risk of osmotic demyelination syndrome.

Background:  The latissimus dorsi (LD) muscle has a dominant pedicle with one thoracodorsal artery and receives sufficient blood by segmental circulation through several perforators. Thus, it is widely used in various reconstructive surgeries. We are reporting on the patterns of the thoracodorsal artery analyzed by chest computed tomography (CT) angiography., Methods:  We analyzed the preoperative chest CT angiography results of 350 patients scheduled to undergo LD flap breast reconstruction following complete mastectomy for breast cancer between October 2011 and October 2020., Results:  A total of 700 blood vessels were classified according to the Kyungpook National University Plastic Surgery-Thoracodorsal Artery (KNUPS-TDA) classification: 388 (185 right and 203 left), 126 (64 right and 62 left), 91 (49 right and 42 left), 57 (27 right and 30 left), and 38 (25 right and 13 left) vessels were classified as type I, type II, type III, type IV, and type V, respectively. Among 350 patients, 205 patients showed matching types for left and right vessels, whereas 145 patients showed mismatching types. For 205 patients with matching types, the distribution by type was 134, 30, 30, 7, and 4 patients with type I, type II, type III, type IV, and type V, respectively. For 145 patients with mismatching types, the distribution by different combinations was 48, 25, 28, 19, 2, 9, 7, 3, 1, and 3 patients with type I + type II, type I + type III, type I + type IV, type I + type V, type II + type III, type II + type IV, type II + type V, type III + type IV, type III + type V, and type IV + type V, respectively., Conclusion:  While there is some diversity in the vascular anatomical structures of the LD flap, the dominant vessel can be found in a similar location in almost all cases and no flap had absence of a dominant vessel. Therefore, in surgical procedures using the thoracodorsal artery as the pedicle, preoperative radiological confirmation is not absolutely necessary; however, due to variants, performing the surgery with an understanding of this aspect should lead to good outcomes., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Fenbendazole (FZ) has potential anti-cancer effects, but its poor water solubility limits its use for cancer therapy. In this study, we investigated the anti-cancer effect of FZ with different drug delivery methods on epithelial ovarian cancer (EOC) in both in vitro and in vivo models., Methods: EOC cell lines were treated with FZ and cell proliferation was assessed. The effect of FZ on tumor growth in cell line xenograft mouse model of EOC was examined according to the delivery route, including oral and intraperitoneal administration. To improve the systemic delivery of FZ by converting fat-soluble drugs to hydrophilic, we prepared FZ-encapsulated poly(D,L-lactide-co-glycolide) acid (PLGA) nanoparticles (FZ-PLGA-NPs). We investigated the preclinical efficacy of FZ-PLGA-NPs by analyzing cell proliferation, apoptosis, and in vivo models including cell lines and patient-derived xenograft (PDX) of EOC., Results: FZ significantly decreased cell proliferation of both chemosensitive and chemoresistant EOC cells. However, in cell line xenograft mouse models, there was no effect of oral FZ treatment on tumor reduction. When administered intraperitoneally, FZ was not absorbed but aggregated in the intraperitoneal space. We synthesized FZ-PLGA-NPs to obtain water solubility and enhance drug absorption. FZ-PLGA-NPs significantly decreased cell proliferation in EOC cell lines. Intravenous injection of FZ-PLGA-NP in xenograft mouse models with HeyA8 and HeyA8-MDR significantly reduced tumor weight compared to the control group. FZ-PLGA-NPs showed anti-cancer effects in PDX model as well., Conclusion: FZ-incorporated PLGA nanoparticles exerted significant anti-cancer effects in EOC cells and xenograft models including PDX. These results warrant further investigation in clinical trials., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2023. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Extracranial vascular malformations are abnormal formations of blood vessels located outside the brain (extracranial) that develop during fetal development. They are caused by errors in the formation of blood vessels in the embryo and can affect various parts of the body, such as the head, neck, face, and other regions. Some malformations may be asymptomatic and only require monitoring, while others may cause significant health issues or cosmetic concerns and may need medical intervention. There are very few studies have investigated the nationwide incidence and quantitative mortality of vascular malformations in terms of their subtypes. Thus, this study aimed to determine the nationwide incidence and mortality associated with vascular malformations. This nationwide population-based study evaluated 70,517 patients with vascular malformations from 2008 to 2021. We evaluated the incidence and mortality associated with each subtype of vascular malformation. Furthermore, Cox regression analysis was used to evaluate the association between vascular malformation and mortality. The annual incidence (per 100,000 population) of overall vascular, venous, capillary, arteriovenous, and lymphatic malformations was 9.85, 1.48, 2.31, 0.24, and 5.82 cases, respectively. Patients with vascular malformations, except those with venous malformations, had higher mortality than the matched controls. Moreover, among the vascular malformation subgroups, the adjusted hazard ratio of mortality was the highest for arteriovenous malformations. This study revealed that the overall annual incidence of vascular malformations was 9.85 cases per 100,000 population in Korea from 2008 to 2021. The mortality of the matched general population was lower than that of patients with vascular malformations, except for those with venous malformations. Additionally, the adjusted hazard ratio for mortality associated with arteriovenous malformations was the highest among the vascular malformation subgroups., (© 2023. Springer Nature Limited.)