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The CLC family encompasses two functional categories of transmembrane proteins: chloride conducting channels and proton-chloride antiporters. All members in this chloride channel/transporter family consist of two identical protein subunits, and each subunit forms an independent ion-transport pathway, a structural architecture known as "double barrel." These CLC proteins serve biological functions ranging from membrane excitability and cell volume regulation to acidification of endosomes. Despite their ubiquitous expression, physiological significance, and resolved molecular structures of some of the family members, the mechanisms governing these molecules' biophysical functions are still not completely settled. However, a series of functional and structural studies have brought insights into interesting questions related to these proteins. This chapter explores the functional peculiarities underlying CLC channels aided by information observed from the chloride-proton antiporters in the CLC family. The overall structural features of these CLC proteins will be presented, and the biophysical functions will be addressed. Finally, the mechanism of pharmacological agents that interact with CLC channels will also be discussed., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease with a complex genetic basis, presenting both in familial and sporadic forms. The hexanucleotide (G 4 C 2 ) repeat expansion in the C9orf72 gene, which triggers distinct pathogenic mechanisms, has been identified as a major contributor to familial and sporadic Amyotrophic lateral sclerosis cases. Animal models have proven pivotal in understanding these mechanisms; however, discrepancies between models due to variable transgene sequence, expression levels, and toxicity profiles complicate the translation of findings. Herein, we provide a systematic comparison of 7 publicly available Drosophila transgenes modeling the G 4 C 2 expansion under uniform conditions, evaluating variations in their toxicity profiles. Further, we tested 3 previously characterized disease-modifying drugs in selected lines to uncover discrepancies among the tested strains. Our study not only deepens our understanding of the C9orf72 G 4 C 2 mutations but also presents a framework for comparing constructs with minute structural differences. This work may be used to inform experimental designs to better model disease mechanisms and help guide the development of targeted interventions for neurodegenerative diseases, thus bridging the gap between model-based research and therapeutic application., Competing Interests: Declaration of Competing Interests The authors have no potential conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Despite the diverse genetic mutations in head and neck cancer, the chemotherapy outcome for this cancer has not improved for decades. It is urgent to select prognostic factors and therapeutic targets for oropharyngeal cancer to establish precision medicine. Recent studies have identified PSMD1 as a potential prognostic marker in several cancers. We aimed to assess the prognostic significance of PSMD1 expression in oropharyngeal squamous cell carcinoma (OPSCC) patients using immunohistochemistry., Methods: We studied 64 individuals with OPSCC tissue from surgery at Seoul National University Bundang Hospital between April 2008 and August 2017. Immunostaining analysis was conducted on the tissue microarray (TMA) sections (4 μm) for p16 and PSMD1. H-score, which scale from 0 to 300, was calculated from each nucleus, cytoplasm, and cellular expression. Clinicopathological data were compared with Chi-squared test, Fisher's exact test, t-test, and logistic regression. Survival data until 2021 were achieved from national statistical office of Korea. Kaplan-Meier method and cox-regression model were used for disease-specific survival (DSS) analysis., Results: H-score of 90 in nucleus was appropriate cutoff value for 'High PSMD1 expression' in OPSCC. Tonsil was more frequent location in low PSMD1 group (42/52, 80.8%) than in high PSMD1 group (4/12, 33.3%; P = .002). Early-stage tumor was more frequent in in low PSMD1 group (45/52, 86.5%) than in high PSMD1 group (6/12, 50%; P = .005). HPV was more positive in low PSMD1 group (43/52, 82.7%) than in high PSMD1 group (5/12, 41.7%; P = .016). Patients with PSMD1 high expression showed poorer DSS than in patients with PSMD1 low expression (P = .006 in log rank test). In multivariate analysis, PSMD1 expression, pathologic T staging, and specimen age were found to be associated with DSS (P = .011, P = .025, P = .029, respectively)., Conclusions: In our study, we established PSMD1 as a negative prognostic factor in oropharyngeal squamous cell carcinoma, indicating its potential as a target for targeted therapy and paving the way for future in vitro studies on drug repositioning., (© 2023. The Author(s).)

A complete blood count (CBC) is routinely ordered for emergency department (ED) patients with infections. Certain parameters, such as the neutrophil-to-lymphocyte ratio (NLR), might have prognostic value. We aimed to evaluate the prognostic value of the presenting CBC parameters combined with clinical variables in predicting 30-day mortality in adult ED patients with infections using an artificial neural network (ANN). We conducted a retrospective study of ED patients with infections between 17 December 2021 and 16 February 2022. Clinical variables and CBC parameters were collected from patient records, with NLR, monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) calculated. We determined the discriminatory performance using the area under the receiver operating characteristic curve (AUROC) and performed a 70/30 random data split and supervised ANN machine learning. We analyzed 558 patients, of whom 144 (25.8%) had sepsis and 60 (10.8%) died at 30 days. The AUROCs of NLR, MLR, PLR, and their sum were 0.644 (95% CI 0.573-0.716), 0.555 (95% CI 0.482-0.628), 0.606 (95% CI 0.529-0.682), and 0.610 (95% CI 0.534-0.686), respectively. The ANN model based on twelve variables including clinical variables, hemoglobin, red cell distribution width, NLR, and PLR achieved an AUROC of 0.811 in the testing dataset., (© 2023. The Author(s).)

Photoplethysmogram (PPG) performs an important role in alarming atrial fibrillation (AF). While the importance of PPG is emphasized, there is insufficient amount of openly available atrial fibrillation PPG data. We propose a U-net-based generative adversarial network (GAN) which synthesize PPG from paired electrocardiogram (ECG). To measure the performance of the proposed GAN, we compared the generated PPG to reference PPG in terms of morphology similarity and also examined its influence on AF detection classifier performance. First, morphology was compared using two different metrics against the reference signal: percent root mean square difference (PRD) and Pearson correlation coefficient. The mean PRD and Pearson correlation coefficient were 27% and 0.94, respectively. Heart rate variability (HRV) of the reference AF ECG and the generated PPG were compared as well. The p -value of the paired t -test was 0.248, indicating that no significant difference was observed between the two HRV values. Second, to validate the generated AF PPG dataset, four different datasets were prepared combining the generated PPG and real AF PPG. Each dataset was used to optimize a classification model while maintaining the same architecture. A test dataset was prepared to test the performance of each optimized model. Subsequently, these datasets were used to test the hypothesis whether the generated data benefits the training of an AF classifier. Comparing the performance metrics of each optimized model, the training dataset consisting of generated and real AF PPG showed a test accuracy result of 0.962, which was close to that of the dataset consisting only of real AF PPG data at 0.961. Furthermore, both models yielded the same F1 score of 0.969. Lastly, using only the generated AF PPG dataset resulted in test accuracy of 0.945, indicating that the trained model was capable of generating valuable AF PPG. Therefore, it can be concluded that the generated AF PPG can be used to augment insufficient data. To summarize, this study proposes a GAN-based method to generate atrial fibrillation PPG that can be used for training atrial fibrillation PPG classification models., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s) 2023.)

The transcription factor YAP-TEAD is the downstream effector of the Hippo pathway which controls cell proliferation, apoptosis, tissue repair, and organ growth. Dysregulation of the Hippo pathway has been correlated with carcinogenic processes. A co-crystal structure of TEAD with its endogenous ligand palmitic acid (PA) as well as with flufenamic acid (FA) has been disclosed. Here we report the development of HC-258, which derives from FA and possesses an oxopentyl chain that mimics a molecule of PA as well as an acrylamide that reacts covalently with TEAD's cysteine. HC-258 reduces the CTGF , CYR61 , AXL , and NF2 transcript levels and inhibits the migration of MDA-MB-231 breast cancer cells. Co-crystallization with hTEAD2 confirmed that HC-258 binds within TEAD's PA pocket, where it forms a covalent bond with its cysteine., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

Introduction: Mesothelioma is an aggressive tumor in the pleural cavity that is difficult to treat. Diagnosis is usually late with minimal treatment options available for the patients and with unfavorable outcomes. However, recent advances in immunotherapy using γδ T cells may have potential against mesothelioma, given its ample tumoricidal and tumor-migratory properties could allow its infiltration to the widespread tumor mass. Thus, we hypothesize that Vδ2 T cells can perform cytotoxic activities against mesothelioma especially when combined with immune checkpoint blocker against PD-1., Methods: Human Vδ2 T cells were expanded from peripheral blood mononuclear cells using Tetrakis-pivaloyloxymethyl 2-(thiazole-2-ylamino) ethylidene-1,1-bisphosphonate (PTA) plus IL-2 for 13 days, before used to test for cytotoxicity against mesothelioma cell lines. Mesothelioma-bearing mice was established by Intrapleural administration of mesothelioma cell lines to test for the efficacy of Vδ2 T cells plus anti-PD-1 antibody combination treatment. Pyroptosis was evaluated by cell morphology, western blot analysis, and ELISA experiments. Flow cytometry was used to examine expression of BTN2A1, BTN3A1, PD-L1, PD-L2 on mesothelioma cell lines. Immunofluorescence staining was performed to detect Vδ2 T cells post adoptive transfer and characteristics of pyroptosis in ex vivo mesothelioma tissue sections., Results: Indeed, our data demonstrated that Vδ2 T cells killing mesothelioma can be enhanced by anti-PD-1 antibody in vitro , especially for high PD-1 expressing cells, and in vivo in the intrapleural mesothelioma mice model established by us. Adoptive transfer of Vδ2 T cells into these mice leads to tumor regression by 30-40% compared to control. Immunofluorescence of the tumor section confirmed infiltration of Vδ2 T cells into the tumor, especially to cells with BTN2A1 expression (a Vδ2 T cell activating molecule) despite PD-L1 co-localization. Interestingly, these cells co-expressed cleaved gasdermin D, suggesting that pyroptosis was induced by Vδ2 T cells. This was verified by Vδ2 T/mesothelioma co-culture experiments demonstrating membrane ballooning morphology, increased cleaved caspase-3 and gasdermin E, and upregulated IL-1β and IL-18., Discussion: Vδ2 T cells plus anti-PD1 exhibited cytotoxicity against mesothelioma in vivo. However, we found no advantage for anti-PD-1 against PD-1 high expressing Vδ2 T cells in promoting pyroptosis. Taken together, our work demonstrated that Vδ2 T cells combined with anti-PD-1 antibody can be developed as a potential combination immunotherapy for mesothelioma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Lui, Ye, Chan, Tanaka and Cheung.)

Cardiovascular diseases (CVDs) are the most common cardiovascular system disorders. Cellular senescence is a key mechanism associated with dysfunction of aged vascular endothelium. Hyaluronic acid and proteoglycan link protein 1 (HAPLN1) has been known to non-covalently link hyaluronic acid (HA) and proteoglycans (PGs), and forms and stabilizes HAPLN1-containing aggregates as a major component of extracellular matrix. Our previous study showed that serum levels of HAPLN1 decrease with aging. Here, we found that the HAPLN1 gene expression was reduced in senescent human umbilical vein endothelial cells (HUVECs). Moreover, a recombinant human HAPLN1 (rhHAPLN1) decreased the activity of senescence-associated β-gal and inhibited the production of senescence-associated secretory phenotypes, including IL-1β, CCL2, and IL-6. rhHAPLN1 also down-regulated IL-17A levels, which is known to play a key role in vascular endothelial senescence. In addition, rhHAPLN1 protected senescent HUVECs from oxidative stress by reducing cellular reactive oxygen species levels, thus promoting the function and survival of HUVECs and leading to cellular proliferation, migration, and angiogenesis. We also found that rhHAPLN1 not only increases the sirtuin 1 (SIRT1) levels, but also reduces the cellular senescence markers levels, such as p53, p21, and p16. Taken together, our data indicate that rhHAPLN1 delays or inhibits the endothelial senescence induced by various aging factors, such as replicative, IL-17A, and oxidative stress-induced senescence, thus suggesting that rhHAPLN1 may be a promising therapeutic for CVD and atherosclerosis.

Background and Purpose: We aimed to determine whether structural brain connectivity is significantly associated with the response to sumatriptan in patients with migraine., Methods: We retrospectively enrolled patients with newly diagnosed migraine who underwent brain diffusion-tensor imaging (DTI) at the time of diagnosis, with regular follow-up for at least 6 months after the initial diagnosis. Patients were classified into good- and poor-responder groups according to their response to sumatriptan. We analyzed the structural connectivity using DTI by applying graph theory using DSI Studio software., Results: We enrolled 59 patients (35 good responders and 24 poor responders) and 30 healthy controls. Global structural connectivity differed significantly between patients with migraine and healthy controls, while local structural connectivity differed significantly between good and poor responders. The betweenness centrality was lower in good responders than in poor responders in the left lateral geniculate thalamic nucleus (26.078 vs. 41.371, p =0.039) and right medial mediodorsal magnocellular thalamic nucleus (60.856 vs. 90.378, p =0.021), whereas was higher in good responders in the left lateral pulvinar thalamic nucleus (98.365 vs. 50.347, p =0.003) and right medial pulvinar thalamic nucleus (216.047 vs. 156.651, p =0.036)., Conclusions: We found that structural connectivity in patients with migraine differed from that in healthy controls. Moreover, the local structural connectivity varied with the response to sumatriptan, which suggests that structural connectivity is a useful factor for predicting how a patient will respond to sumatriptan., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2023 Korean Neurological Association.)

Background: Although vitamin D is one of the essential nutrients associated with musculoskeletal system function, there is no standard treatment method for vitamin D deficiency. This study aimed to investigate the effects of vitamin D supplementation on the improvement in symptoms, functional recovery of the spine, and changes in the quality of life in patients with spinal stenosis., Methods: In this prospective study, patients with spinal stenosis and serum 25-hydroxy vitamin D levels < 10 ng/mL were randomly assigned to a supplementation group (Group S) and a non-supplementation group (Group NS): 26 participants in Group S (16 females and 10 males) and 25 in Group NS (15 females and 10 males). The degree of lower back pain in both groups was assessed using the visual analog scale; spine function was assessed using the Oswestry disability index and Roland-Morris disability questionnaire; and patient quality of life was assessed using the 36-item short form health survey. We compared and analyzed the values that were measured at baseline, between 4 and 6 weeks (V1), 10 and 12 weeks (V2), and 22 and 26 weeks (V3)., Results: No statistically significant difference was observed in lower back pain, spine function, or quality of life between both groups at baseline. In terms of lower back pain in V1, Group S scored 4.15 ± 3.12, while Group NS scored 5.64 ± 1.85 (P = .045). In V2, Group S scored 3.15 ± 2.38, while Group NS scored 4.52 ± 1.87 (P = .027). Moreover, in V3, Group S scored 3.58 ± 1.65, while Group NS scored 4.60 ± 1.68 (P = .033), indicating a statistically significant improvement in each period., Conclusion: If a vitamin D deficiency that does not require surgical treatment exists in patients with lumbar spinal stenosis, high-dose vitamin D injections can improve lower back pain, which is the main symptom of lumbar spinal stenosis, as well as the functional outcomes of the spine and quality of life., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Methotrexate (MTX) is an anchor drug for most patients with rheumatoid arthritis (RA); however, its use may be limited depending on renal function. Therefore, this study aimed to examine the discrepancy in the estimated glomerular filtration rate (eGFR) using conventional serum creatinine (SCr)-, cystatin C-, and MTX-associated toxicities in patients with RA., Methods: In total, 436 patients were enrolled, and eGFR was evaluated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on both cystatin C and SCr levels. The CKD and MTX dosing stages were classified according to eGFR. MTX-associated toxicities were also evaluated., Results: The mean eGFR using CKD-EPI cystatin C (CKD-EPI cys ) was 89.44 mL/min/1.73 m 2 , lower than the eGFR using CKD-EPI SCr (CKD-EPI SCr ) of 95.55 mL/min/1.73 m 2 . After converting eGFR to CKD-EPI cys by CKD-EPI SCr , 29.8% of patients were reclassified to a higher stage according to the Kidney Disease: Improving Global Outcomes CKD stage. Also, according to the MTX guidelines, 6.4% of the group with an eGFR > 50 mL/min/1.73 m 2 were reclassified to eGFR 10-50 mL/1.73 m 2 , requiring dose adjustment. The incidence of MTX-associated toxicities, such as anemia, leukopenia, and nephrotoxicity, was significantly higher in the CKD stage-changed group than in the nonstage-changed group., Conclusion: Our results showed that eGFR based on SCr was overestimated compared with eGFR based on cystatin C. In addition, we demonstrated that MTX-associated toxicities were significantly increased in the group with a changed stage when the eGFR was converted from CKD-EPI SCr to CKD-EPI cys .

In this study, gametotoxicity and embryotoxicity experiments were performed using Hemicentrotus pulcherrimus to investigate the toxic effects of tributyltin (TBT). The effects of TBT on fertilization and embryogenesis were assessed at various concentrations (0, 0.02, 0.05, 0.09, 0.16, 0.43, 0.73, 4.68, and 9.22 ppb). The fertilization rates decreased in a concentration-dependent manner, with significant reduction following treatment with TBT at 0.05 ppb. Embryos exhibited developmental impairment after TBT exposure at each tested concentration. The frequency of developmental inhibition delay that treatment with TBT delayed embryonic development in a dose-dependent manner, with 100% of embryos exhibiting developmental impairment at 4.68 ppb. During developmental recovery tests, embryos cultured in fresh media without TBT showed advanced embryonic development. Although the observed normal development after transferring the developmentally delayed embryos to fresh media without TBT offers prospects for the restoration of contaminated environments, embryonic development remained incomplete. These results suggest that TBT adversely affects the early embryonic development of H. pulcherrimus .

Introduction: To investigate the safety and effectiveness of insulin degludec (IDeg) in a real-world population of Korean patients with diabetes requiring insulin therapy., Methods: This was a multicenter, prospective, single-arm, open-label, non-interventional study. Patients aged ≥ 12 months and treated with previous glucose-lowering medications were eligible to switch to IDeg. The primary endpoint was the incidence of adverse events (AEs), and the secondary endpoints were changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial glucose (PPG), and target HbA1c < 7.0%., Results: In total, 3225 and 2450 patients were included in the safety analysis set (SAS) and effectiveness analysis set (EAS), respectively. The mean baseline HbA1c and duration of diabetes were 9.4% and 13.0 years, respectively. Adverse events were reported in 740 patients (22.9%); the majority were mild and resolved. Significant improvements were observed in HbA1c, FPG, and PPG at week 26 (all p < 0.0001). The target of HbA1c < 7% was achieved in 22.2% of patients at week 26., Conclusion: In real-world clinical practice, 26 weeks of IDeg treatment resulted in significant reductions in glycemic parameters with a low incidence of AEs in Korean patients with diabetes. No new safety signals were observed., Clinical Trials Registry and Registration Number: This trial is registered under ClinicalTrials.gov (NCT02779413) and the universal trial number is [U1111-1176-2287]., (© 2023. The Author(s).)

The fifth subfraction of low-density lipoprotein (L5 LDL) can be separated from human LDL using fast-protein liquid chromatography with an anion exchange column. L5 LDL induces vascular endothelial injury both in vitro and in vivo through the lectin-like oxidized LDL receptor-1 (LOX-1). However, no in vivo evidence shows the tendency of L5 LDL deposition on vascular endothelium and links to dysfunction. This study aimed to investigate L5 LDL retention in vivo using SPECT/CT imaging, with Iodine-131 ( 131 I)-labeled and injected into six-month-old apolipoprotein E knockout (apoE -/- ) mice through tail veins. Besides, we examined the biodistribution of L5 LDL in tissues and analyzed the intracellular trafficking in human aortic endothelial cells (HAoECs) by confocal microscopy. The impacts of L5 LDL on HAoECs were analyzed using electron microscopy for mitochondrial morphology and western blotting for signaling. Results showed 131 I-labeled-L5 was preferentially deposited in the heart and vessels compared to L1 LDL. Furthermore, L5 LDL was co-localized with the mitochondria and associated with mitofusin (MFN1/2) and optic atrophy protein 1 (OPA1) downregulation, leading to mitochondrial fission. In summary, L5 LDL exhibits a propensity for subendothelial retention, thereby promoting endothelial dysfunction and the formation of atherosclerotic lesions., 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 B.V. All rights reserved.)

Current additive manufacturing processes for polymers, including material extrusion, vat photopolymerization, material jetting, and powder bed fusion, have limitations in manufacturing high-temperature thermoplastics including narrow material selection, compromised mechanical properties, and potential degradation of materials during processing. Polysulfone (PSU) is a high-temperature thermoplastic with outstanding chemical resistance, flame retardancy, and toughness. However, besides injection molding, additive manufacturing of PSU has only been achieved through extrusion or solvent-cast three-dimensional (3D) printing without obtaining high mechanical properties. In this work, precipitation printing is applied to fabricate high-temperature thermoplastics such as PSU for the first time, where tailoring of the microstructure and mechanical properties is enabled through control of solvents and printing parameters. The printed PSU can either be dense and strong with 2.47 GPa Young's modulus and 70.6 MPa tensile strength or porous and highly anisotropic. After drying at a maximum temperature of 190 °C, both the printed dense and porous PSU samples have a glass-transition temperature of about 200 °C, which allows them to be used in high-temperature environments. Thus, precipitation printing provides an alternative approach to manufacture high-temperature thermoplastics like PSU with scalability and tailorable properties.

Iridium(I)-catalyzed regioselective B(4)-alkenylation has been developed from o -carboranyl sulfoxonium ylides and alkynes through B(4)-H activation. The sequential B(4)- and B(6)-alkenylation afforded B(3,5)-dialkenylated o -carboranyl sulfoxonium ylides in one pot. Eventually, two alkenyl groups, the same or different, were introduced at positions 3 and 5 of the carborane. Sulfoxonium ylide used as a directing group remains available for further functionalization and is converted to B-alkenylated o -carboranyl trichloromethyl ketones.

Waterborne polyurethane-acrylate (WPUA) grafted with polyurethane was prepared to improve the film-forming ability of hard-type acrylic latex. To balance the film-formation ability and hardness, the WPUA latex was designed with a hard core (polyacrylate) and soft shell (polyurethane). The grafting ratio was controlled through varying the content of 2-hydroxyethyl methacrylate (HEMA) used to cap the ends of the polyurethane prepolymer. The morphologies of the latex particles, film surface, and fracture surface of the film were characterized through transmission electron microscopy, atomic force microscopy, and scanning electron microscopy, respectively. An increase in the grafting ratio resulted in the enhanced miscibility of polyurethane and polyacrylate but reduced adhesion between particles and increased minimum film formation temperature. In addition, grafting was essential to obtain transparent WPUA films. Excessive grafting induced defects such as micropores within the film, leading to the decreased hardness and adhesive strength of the film. The optimal HEMA content for the preparation of a WPUA coating with excellent film-forming ability and high hardness in ambient conditions was noted to be 50%. The final WPUA film was prepared without coalescence agents that generate volatile organic compounds.

This study aimed to determine the feasibility of temperature difference as an overgrowth-prevention technique to influence plant height and internode length in a plant factory with artificial lighting. The control plants were grown in a commercial nursery greenhouse using a growth regulator (Binnari), and +DIF (25 °C/15 °C), 0DIF (20 °C/20 °C), and -DIF (15 °C/25 °C) were the treatments with different day/night temperatures and the same average temperature (20 °C). Cucumbers showed the strongest suppression under the -DIF treatment, with a dwarfism rate of 33.3%. Similarly, tomatoes showed 0.8% and 22.2% inhibition in the 0DIF and -DIF treatments, respectively. The F V /F M of cucumber was approximately 0.81 for all treatments. The OJIP changes differed for cucumbers; however, both cucumbers and tomatoes had similar OJIP curve patterns and no abnormalities. The relative growth rate of cucumbers at the growth stage was 1.48 cm·cm·day -1 for days 6-9 in +DIF stage 3, which was the highest growth rate among all treatments, and 0.71 cm·cm·day -1 for days 3-6 in -DIF stage 1, which was the most growth-inhibited treatment. In tomatoes, we found that days 3-6 of -DIF stage 1 had the most growth inhibition at 0.45 cm·cm·day -1 . For cucumber, -DIF days 3-6 had the most growth inhibition, with a relative growth rate of 0.71 cm·cm·day -1 , but the fidelity was significantly higher than the other treatments, with a 171% increase. The same was true for tomatoes, with days 3-6 of -DIF stage 1 showing the most inhibited growth at 0.45 cm·cm·day -1 but a 200% increase in fidelity. Therefore, applying the -DIF treatment at the beginning of growth would be most effective for both cucumbers and tomatoes to prevent overgrowth through the DIF in a plant factory with artificial lighting because it does not interfere with the seedling physiology and slows down the growth and development stage.

Aims: To evaluate the effect of dapagliflozin on body composition such as total body fat (BF) mass, abdominal visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) areas compared with glimepiride in Korean patients with type 2 diabetes., Materials and Methods: This was a 52-week, multicentre, randomized, parallel-group, open-label, Phase IV (NCT02564926) study. Patients with inadequate glycaemic control (glycated haemoglobin ≥7.0% and <10.0%) on metformin monotherapy (≥1000 mg/day) were randomized 1:1 to receive dapagliflozin 10 mg/day or glimepiride 1-2 mg/day for 12 months as an add-on to metformin. Baseline and end of study body composition evaluations included dual-energy X-ray absorptiometry and abdominal computed tomography scans., Results: Of 124 enrolled patients from 14 centres, 121 received study treatment (dapagliflozin: 60; glimepiride: 61) and 106 (85.5%) completed the study. Over 52 weeks, the dapagliflozin group showed the following differences versus the glimepiride group: -2.59 kg BF mass, -1.94% BF%, -17.55 cm 2 VAT area, -18.39 cm 2 SAT area, -0.46% glycated haemoglobin, -18.25 mg/dl fasting blood glucose, -3.7 kg weight, -2.21 cm waist circumference, -1.37 kg/m 2 body mass index, -6.81 mmHg systolic blood pressure and +657.71 ng/ml in adiponectin; all were statistically significant. Both groups had similar incidences of adverse events; however, hypoglycaemic events were mainly (12 of 15) reported in the glimepiride group., Conclusion: Dapagliflozin reduced total BF mass, abdominal VAT and SAT areas, and showed better glycaemic control than glimepiride. Being safe and well-tolerated, dapagliflozin appears to be a more favourable alternative to sulphonylureas as add-on therapy after metformin monotherapy failure in Korean patients with type 2 diabetes., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Hair loss is a common condition that can have a negative impact on an individual's quality of life. The severe side effects and the low efficacy of current hair loss medications create unmet needs in the field of hair loss treatment. Hyaluronan and Proteoglycan Link Protein 1 (HAPLN1), one of the components of the extracellular matrix, has been shown to play a role in maintaining its integrity. HAPLN1 was examined for its ability to impact hair growth with less side effects than existing hair loss treatments. HAPLN1 was predominantly expressed in the anagen phase in three stages of the hair growth cycle in mice and promotes the proliferation of human hair matrix cells. Also, recombinant human HAPLN1 (rhHAPLN1) was shown to selectively increase the levels of transforming growth factor-β receptor II in human hair matrix cells. Furthermore, we observed concomitant activation of the ERK1/2 signaling pathway following treatment with rhHAPLN1. Our results indicate that rhHAPLN1 elicits its cell proliferation effect via the TGF-β2-induced ERK1/2 pathway. The prompt entering of the hair follicles into the anagen phase was observed in the rhHAPLN1-treated group, compared to the vehicle-treated group. Insights into the mechanism underlying such hair growth effects of HAPLN1 will provide a novel potential strategy for treating hair loss with much lower side effects than the current treatments.

Objective: When evaluating individuals with the same parent and no phenotype by pedigree best linear unbiased prediction (BLUP), it is difficult to explain carcass grade difference and select individuals because they have the same value in pedigree BLUP (PBLUP). However, single step GBLUP (ssGBLUP), which can estimate the breeding value suitable for the individual by adding genotype, is more accurate than the existing method., Methods: The breeding value and accuracy were estimated with pedigree BLUP and ssGBLUP using pedigree and genotype of 408 Hanwoo cattle from 16 families with the same parent among siblings produced by fertilized egg transplantation. A total of 14,225 Hanwoo cattle with pedigree, genotype and phenotype were used as the reference population. PBLUP obtained estimated breeding value (EBV) using the pedigree of the test and reference populations, and ssGBLUP obtained genomic EBV (GEBV) after constructing and H-matrix by integrating the pedigree and genotype of the test and reference populations., Results: For all traits, the accuracy of GEBV using ssGBLUP is 0.18 to 0.20 higher than the accuracy of EBV obtained with PBLUP. Comparison of EBV and GEBV of individuals without phenotype, since the value of EBV is estimated based on expected values of alleles passed down from common ancestors. It does not take Mendelian sampling into consideration, so the EBV of all individuals within the same family is estimated to be the same value. However, GEBV makes estimating true kinship coefficient based on different genotypes of individuals possible, so GEBV that corresponds to each individual is estimated rather than a uniform GEBV for each individual., Conclusion: Since Hanwoo cows bred through embryo transfer have a high possibility of having the same parent, if ssGBLUP after adding genotype is used, estimating true kinship coefficient corresponding to each individual becomes possible, allowing for more accurate estimation of breeding value.

This study aimed to examine change in the graft bending angle (GBA) according to various knee flexion angles in creating femoral tunnel by the transportal technique in ACL reconstruction, and to reveal knee flexion angle minimizing GBA while maintaining stable femoral tunnel characteristics. Patients who underwent ACL reconstruction using the transportal technique between January 2017 and December 2018 were retrospectively reviewed. Patients were classified into three groups according to knee flexion angle when creating femoral tunnel (group 1: < 120° (n = 19); group 2: 120-129° (n = 32); group 3: ≥ 130° (n = 33). GBA was measured on three-dimensional knee model reconstructed from postoperative computed tomography images. The length of the femoral tunnel and posterior wall blow-out were also checked. There was significant difference of GBA between the groups (group 1 = 112.1°; group 2 = 106.4°; group 3 = 101.4°, p < 0.001). The knee flexion angle in creating femoral tunnel was negatively correlated with GBA (r = - 0.733, p < 0.001). Five patients in group 1 had short femoral tunnel. GBA was influenced by knee flexion angle in creating femoral tunnel and got more acute as the knee flexion angle increased. Considering length and risk of wall blow-out in femoral tunnel, and GBA, knee flexion angle between 120 and 130° could be recommended as appropriate angle to create optimal femoral tunnel in ACL reconstruction using the transportal technique., (© 2023. Springer Nature Limited.)

Iridium(III)-catalyzed C-H cyclization of sulfoximines with diazo Meldrum's acid provided cyclic sulfoximines with a carbonyl group in good to excellent yields. These compounds were easily converted into unsubstituted and arylated sulfoximines. Moreover, the vinyl triflates obtained from the cyclic sulfoximines underwent palladium(II)-catalyzed cross-coupling reactions with a variety of aryl, arylalkynyl, and heteroatom (N and S) nucleophiles, affording a wide range of monosubstituted sulfoximines in high yields.

Iridium(III)-catalyzed regioselective B(4)-H amination is developed from the reaction of o -carborane acids with sulfilimines without any oxidants under mild conditions, which leads to a wide range of B(4)-H aminated o -carboranes in good yields with a broad substrate scope. Moreover, the selective B(3,6)-diamination reaction of the o -carborane acid was achieved. The present reaction is attractive from a practical point of view because dibenzothiophene is quantitatively recovered and reused.

PPARα corepressor NCoR1 is a key regulator of fatty acid β-oxidation and ketogenesis. However, its regulatory mechanism is largely unknown. Here, we report that oncoprotein p21-activated kinase 4 (PAK4) is an NCoR1 kinase. Specifically, PAK4 phosphorylates NCoR1 at T1619/T2124, resulting in an increase in its nuclear localization and interaction with PPARα, thereby repressing the transcriptional activity of PPARα. We observe impaired ketogenesis and increases in PAK4 protein and NCoR1 phosphorylation levels in liver tissues of high fat diet-fed mice, NAFLD patients, and hepatocellular carcinoma patients. Forced overexpression of PAK4 in mice represses ketogenesis and thereby increases hepatic fat accumulation, whereas genetic ablation or pharmacological inhibition of PAK4 exhibites an opposite phenotype. Interestingly, PAK4 protein levels are significantly suppressed by fasting, largely through either cAMP/PKA- or Sirt1-mediated ubiquitination and proteasome degradation. In this way, our findings provide evidence for a PAK4-NCoR1/PPARα signaling pathway that regulates fatty acid β-oxidation and ketogenesis., (© 2023. Springer Nature Limited.)

The continuous production of high-strength nanocellulose long filaments (NCLFs) is critical in natural fiber-reinforced polymer composites. Despite the widespread availability of numerous filament production processes, the cost-effective and continuous fabrication of high-strength NCLFs on a large scale remains an ongoing challenge. Herein, we present an integrated wet-spinning system by incorporating a few previously researched filament production techniques to mass fabricate high-strength continuous NCLFs. The spinning speed is increased to improve NCLF productivity, and the bobbin winder speeds, collector bobbin winder location, and NCLF drying conditions are tuned. At the spinning speed of 510 cm/min, a production rate of 4.99 m/min is achieved, five times higher than the productivity of the former pilot system (0.92 m/min). Moreover, an AC electric field and mechanical stretching are introduced to highlight the versatility of the proposed integrated wet-spinning system, thereby enhancing the mechanical properties of NCLFs., (© 2023. Springer Nature Limited.)

Herein, a novel biomass-derived itaconic acid (IA)-based epoxy acrylate oligomer (EAO) is synthesized by means of the esterification reaction of the epoxy group of bisphenol A diglycidyl ether (BADGE) with the carboxylic group of IA. The detailed chemical structure of the as-prepared bisphenol A diglycidyl ether diitaconate (BI) is characterized via the KOH value, FT-IR spectrum, and 1 H-NMR spectrum. Further, a dual-cure adhesive system is formulated using BADGE, acrylic acid, and trimethylolpropane triacrylate with various BI contents, and the adhesive performance is investigated by measuring the thermal stability, adhesive properties, pencil hardness, and surface energy properties. Thus, the dual-cure adhesive with a BI content of 0.3 mol is shown to provide excellent thermal stability, along with an adhesive strength of 10.7 MPa, a pencil hardness of 2H, and a similar surface energy to that of a typical polycarbonate film. In addition, the properties of the BI-based dual-cure adhesive are compared with those of the dual-cure adhesives based on bisphenol A glycerolate diacrylate or bisphenol A glycerolate dimethacrylate.

Multilayer graphene has attracted significant attention because its physical properties can be tuned by stacking its layers in a particular configuration. To apply the intriguing properties of multilayer graphene in various optoelectronic or spintronic devices, it is essential to develop a synthetic method that enables the control of the stacking configuration. This review article presents the recent progress in the synthesis of multilayer graphene by chemical vapor deposition (CVD). First, we discuss the CVD of multilayer graphene, utilizing the precipitation or segregation of carbon atoms from metal catalysts with high carbon solubility. Subsequently, we present novel CVD approaches to yield uniform and thickness-controlled multilayer graphene, which goes beyond the conventional precipitation or segregation methods. Finally, we introduce the latest studies on the control of stacking configurations in bilayer graphene during CVD processes.

Natural gas plays an important role in daily life and the petrochemical industry, but there are often large amounts of impurities which prevent the full use of methane in natural gas. Developing excellent adsorbents to purify CH 4 from multi-component mixtures is crucial, but also faces great challenges. Here, by utilizing a ligand conformation preorganization strategy, we employ a flexible nonplanar hexacarboxylate ligand with C 2 symmetry to successfully construct a robust microporous metal-organic framework {[Cu 3 (bmipia)(H 2 O) 3 ]·(DMF)(CH 3 CN) 2 } n (GNU-1, bmipia = 5-[ N , N -bis(5-methylisophthalic acid)amion] isophthalate) with an unprecedented topology. More importantly, the obtained GNU-1 not only exhibits good stability in acid-base and water environments, but also shows potential utility as an adsorbent for efficient separation and purification of natural gas under ambient conditions. The adsorption isotherms of GNU-1a (activated GNU-1) exhibit strong binding affinities for C 2 H 6 and C 3 H 8 , a remarkable uptakes of C 3 H 8 (6.64 mmol g -1 ) and C 2 H 6 (4.6 mmol g -1 ) and an excellent selectivity of 330.1 and 17.5 for C 3 H 8 /CH 4 and C 2 H 6 /CH 4 mixtures, respectively, at 298 K and 1 bar. The breakthrough experiments demonstrate that the ternary CH 4 /C 2 H 6 /C 3 H 8 mixtures are completely separated using a fixed-bed separator packed with GNU-1a at ambient temperature and also show great potential for recovering the C 2 H 6 and C 3 H 8 contents from natural gas. Finally, Grand Canonical Monte Carlo simulations are adopted to ascertain potential gas adsorption mechanisms. This work proves the feasibility of optimizing the structure and pore size of MOF materials by regulating the conformation of ligands for application in the field of light hydrocarbon adsorption/separation.

Longitudinal studies on upper respiratory tract microbiome in coronavirus disease 2019 (COVID-19) without potential confounders such as antimicrobial therapy are limited. The objective of this study is to assess for longitudinal changes in the upper respiratory microbiome, its association with disease severity, and potential confounders in adult hospitalized patients with COVID-19. Serial nasopharyngeal and throat swabs (NPSTSs) were taken for 16S rRNA gene amplicon sequencing from adults hospitalized for COVID-19. Alpha and beta diversity was assessed between different groups. Principal coordinate analysis was used to assess beta diversity between groups. Linear discriminant analysis was used to identify discriminative bacterial taxa in NPSTS taken early during hospitalization on need for intensive care unit (ICU) admission. A total of 314 NPSTS samples from 197 subjects (asymptomatic = 14, mild/moderate = 106, and severe/critical = 51 patients with COVID-19; non-COVID-19 mechanically ventilated ICU patients = 11; and healthy volunteers = 15) were sequenced. Among all covariates, antibiotic treatment had the largest effect on upper airway microbiota. When samples taken after antibiotics were excluded, alpha diversity (Shannon, Simpson, richness, and evenness) was similar across severity of COVID-19, whereas beta diversity (weighted GUniFrac and Bray-Curtis distance) remained different. Thirteen bacterial genera from NPSTS taken within the first week of hospitalization were associated with a need for ICU admission (area under the receiver operating characteristic curve, 0.96; 95% CI, 0.91-0.99). Longitudinal analysis showed that the upper respiratory microbiota alpha and beta diversity was unchanged during hospitalization in the absence of antimicrobial therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ling, Lai, Lui, Yeung, Chan, Cheuk, Cheung, Chang, Chiu, Zhang, Wong, Hui, Wong, Chan and Chen.)

Background: For uniportal video-assisted thoracoscopic surgery (VATS), which is greatly dependent on satisfactory lung collapse without lung compression from another port, few reports have elucidated the intraoperative efficacy of bronchial blockers (BBs). We hypothesized that operation time would be prolonged if BBs required more intraoperative repositioning during surgical manipulation. We compared the operation times of different surgical procedures performed using BBs with double-lumen tubes (DLTs) in uniportal VATS., Materials and Methods: Patients who underwent intubated uniportal VATS were enrolled retrospectively from March to May 2019. Data on the patient, anesthetic, and surgical factors were collected. Regression analyses were performed to determine the effect of various factors on operation time., Results: 317 patients who underwent uniportal VATS were included. Wedge resection constituted 70.7%, and anatomic resection constituted 29.3% of procedures. BBs were applied for left- and right-side wedge resection (85.6% and 78.7%, respectively) and left- and right-side anatomic resection (74.1% and 56.4%, respectively). The surgical factors significantly affecting operation time were operation procedures (P < .01), number of lymph nodes sampled (P < .001), and size of tumors (P < .01)., Conclusions: The efficacy of BBs was comparable to that of DLTs for uniportal VATS wedge resection. With significantly less preference for right-side anatomic resection, the efficacy of DLTs was comparable with that of BBs, which were applied in more than half of right-side uniportal anatomic VATS. We conclude that even in uniportal VATSs, rigid-angled BBs demonstrate comparable efficacy with feasible alternatives.

Purpose: With the advancement of deep neural networks in biosignals processing, the performance of automatic sleep staging algorithms has improved significantly. However, sleep staging using only non-electroencephalogram features has not been as successful, especially following the current American Association of Sleep Medicine (AASM) standards. This study presents a fine-tuning based approach to widely generalizable automatic sleep staging using heart rate and movement features trained and validated on large databases of polysomnography., Methods: A deep neural network is used to predict sleep stages using heart rate and movement features. The model is optimized on a dataset of 8731 nights of polysomnography recordings labeled using the Rechtschaffen & Kales scoring system, and fine-tuned to a smaller dataset of 1641 AASM-labeled recordings. The model prior to and after fine-tuning is validated on two AASM-labeled external datasets totaling 1183 recordings. In order to measure the performance of the model, the output of the optimized model is compared to reference expert-labeled sleep stages using accuracy and Cohen's κ as key metrics., Results: The fine-tuned model showed accuracy of 76.6% with Cohen's κ of 0.606 in one of the external validation datasets, outperforming a previously reported result, and showed accuracy of 81.0% with Cohen's κ of 0.673 in another external validation dataset., Conclusion: These results indicate that the proposed model is generalizable and effective in predicting sleep stages using features which can be extracted from non-contact sleep monitors. This holds valuable implications for future development of home sleep evaluation systems., Competing Interests: Competing interestsJoonnyong Lee declares conflicts of interest as the CEO of Mellowing Factory Co. Ltd., which is developing a home sleep monitor. Hee Chan Kim declares conflicts of interest as an investor of Mellowing Factory Co. Ltd. Yu Jin Lee declares no conflicts of interest. Saram Lee declares conflicts of interest as an investor of Mellowing Factory Co. Ltd., (© The Author(s) 2023.)

Sepsis-induced acute kidney injury (AKI) is a common complication in critically ill patients, often resulting in high rates of morbidity and mortality. Previous studies have demonstrated the effectiveness of casein kinase 2 alpha (CK2α) inhibition in ameliorating ischemia-reperfusion-induced AKI. In this study, our aim was to investigate the potential of the selective CK2α inhibitor, 4,5,6,7-tetrabromobenzotriazole (TBBt), in the context of sepsis-induced AKI. To assess this, we initially confirmed an upregulation of CK2α expression following a cecum ligation and puncture (CLP) procedure in mice. Subsequently, TBBt was administered to a group of mice prior to CLP, and their outcomes were compared to those of sham mice. The results revealed that, following CLP, the mice exhibited typical sepsis-associated patterns of AKI, characterized by reduced renal function (evidenced by elevated blood urea nitrogen and creatinine levels), renal damage, and inflammation (indicated by increased tubular injury score, pro-inflammatory cytokine levels, and apoptosis index). However, mice treated with TBBt demonstrated fewer of these changes, and their renal function and architecture remained comparable to that of the sham mice. The anti-inflammatory and anti-apoptotic properties of TBBt are believed to be associated with the inactivation of the mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signaling pathways. In conclusion, these findings suggest that inhibiting CK2α could be a promising therapeutic strategy for treating sepsis-induced AKI.

Background: The aim of this study was to investigate the clinical characteristics of nontuberculous mycobacterial tenosynovitis and to report the process of diagnosis and the outcomes of surgical debridement and drug administration in South Korea., Methods: Between 2010 and 2019, 23 patients (10 men and 13 women) with nontuberculous tenosynovitis of the hand were treated at two centers. Their average age was 64 years, and the average duration of symptoms was 8 months (range, 1-36 months). Eight patients had a history of trauma or surgery. The average number of corticosteroid injections before diagnosis was 2.6 for 7 patients. All 23 patients were treated with a combination of extensive tenosynovectomy and antibiotics., Results: Of the 23 patients, 20 were available for the final follow-up (1, lost to follow-up; 1, transferred to another hospital; and 1, died from a comorbidity). The most common species was Mycobacterium intracellulare (70%), followed by Mycobacterium abscessus (10%). The frequency of involvement of the extensor/flexor tendon was similar to that of the wrist/finger. The mean number of surgical debridement operations was 2.2. The average duration of antibiotic administration was 9.8 months. At the last follow-up, 3 patients were symptom-free with full range of motion at the involved site, 1 patient complained of localized swelling or pain with full range of motion, 1 patient was found to have a recurrence of infection in a finger, and 15 complained of restricted joint motion., Conclusions: The most common species noted in patients with nontuberculous mycobacterial tenosynovitis was M. intracellulare . Patients with only 1 finger involved showed good range of motion at the final follow-up. Most patients experienced delayed wound healing and adverse effects from drug therapy during treatment and limited joint motion at the final follow-up., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2023 by The Korean Orthopaedic Association.)

Objectives : Depressive symptoms are common among older adults and many of them did not seek for professional help. Although Zentangle has been widely implemented in service centers for older adults in many societies, very limited empirical study has been conducted on the effects of this method. This study aims to evaluate the effects of Zentangle on community-dwelling older adults with depressive symptoms. Methods : A randomised waitlist-controlled trial of Zentangle was conducted. Forty-six community-dwelling older adults with mild to moderate depression were recruited and randomly assigned to a six session Zentangle group or a waitlist control group. The effects were examined by comparing the participants who received a six-week Zentangle intervention with those in the waitlist control group. Patient Health Questionnaire (PHQ-9), Self-compassion Scale - Short form (SCS-SF) and other mental health outcomes were assessed at baseline, post-intervention and six-week follow-up. Results : Repeated measure ANOVA revealed significant Time x Group effects for depression (F (2, 88) = 21.29, p < .001) and self-compassion (F (2, 88) = 18.50, p < .001) with a large net effect size. Six-week follow-up indicated that such improvements were sustained. Conclusion : This study provides preliminary support that the Zentangle programme is an effective alternative treatment approach for older adults with mild to moderate depression. The original Zentangle method can reduce depressive symptoms and cultivate self-compassion. Further research is necessary to expand our understanding of the underlying mechanisms of how the original Zentangle method works. Trial registration : ISRCTN66410347., Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-023-04536-x., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Hearing loss in older people can cause communication impairments, decreased quality of life, social isolation, depression, and dementia. Cochlear implant surgery is an effective treatment for older patients with hearing loss who cannot achieve satisfactory audiologic outcomes with hearing aids. However, older people have an increased risk of heart disease and often take medications that affect heart rhythm. Herein, we report a case of an 80-year-old woman who underwent cardioversion at 50J after cochlear implant surgery. Electrical impedance before and after cardioversion showed only minor changes without abnormality, and the cochlear implant functioned well. We believe that the electronic circuits of the cochlear implant may have been relatively tolerant to the electrical shock from the external defibrillator. Typically, cardioversion should be avoided in cochlear implant recipients because it may damage the implant. If cardioversion cannot be avoided, we strongly recommend starting cardioversion at the lowest energy level (50 J) and removing the sound processor of the implant during the procedure.

Purpose: To investigate the quantitative characteristics of anastomoses of macular neovascularization (MNV) in neovascular age-related macular degeneration using optical coherence tomography angiography according to the frequency of intravitreal injections., Methods: Eighty-six eyes of 86 patients treated for neovascular age-related macular degeneration were classified into two groups based on the number of intravitreal injections administered over 12 months: stable (<3) and unstable (≥3). Anastomotic areas were defined as areas surrounded by neighboring vessels in the MNV; their total number, mean area, maximal and minimal diameters (i.e., maximal and minimum Feret diameters), and ratio (Feret aspect ratio) were analyzed in the inner and outer areas of the MNV., Results: Forty-four and 42 eyes were classified into the stable and unstable groups, respectively. The eyes in the unstable group had larger anastomotic areas with longer minimum Feret diameters and longer perimeters in the outer MNV. In the logistic regression analysis, instability was associated with a larger anastomotic area and a longer minimum Feret diameter in the outer MNV. Multivariate analysis revealed that a longer minimum Feret diameter in the outer MNV was the most significant factor ( P = 0.03)., Conclusion: The quantitative characteristics of the anastomotic areas in the MNV might indicate the need for intravitreal injections in patients with neovascular age-related macular degeneration.

Background: In this study, we prepared and evaluated an injectable poloxamer (P407) hydrogel formulation for intratympanic (IT) delivery of dexamethasone (DEX)., Methods: DEX-loaded P407 hydrogels were characterized in terms of thermogelation, drug loading capacities, particle size, and drug release. The in vivo toxicity and drug absorption of the DEX-loaded P407 formulation after IT injection were evaluated using an animal model by performing histopathological analysis and drug concentration measurements., Results: The P407 hydrogel effectively solubilized hydrophobic DEX and demonstrated a sustained release compared to the hydrophilic DEX formulation. The in vivo study showed that the hydrogel formulation delivered considerable drug concentrations to the inner ear and displayed a favorable safety profile without apparent cytotoxicity or inflammation., Conclusion: P407 hydrogel can be useful as an injectable inner ear delivery formulation for hydrophobic drugs due to their biocompatibility, drug-solubilizing capacity, thermogelation, and controlled release., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Purpose: The aims of this study were to identify (1) the spectrum of ictal-interictal continuum (IIC) using the two dimensions of 2HELPS2B score and background suppression and (2) the response to subsequent anti-seizure drugs depends on the spectrum of IIC., Methods: The study prospectively enrolled 62 patients with IIC on EEG. The diagnosis of nonconvulsive status epilepticus was attempted with Salzburg criteria as well as clinical and neuroimaging data. IICs were dichotomized into patients with nonconvulsive status epilepticus and coma-IIC. The 2HELPS2B score was evaluated as the original proposal. The suppression ratio was analyzed with Persyst software., Results: Forty-seven cases (75.8%) were nonconvulsive status epilepticus-IIC and 15 cases (24.2%) were coma-IIC. Multivariate analysis revealed that the 2HELPS2B score was the only significant variable dichotomizing the spectrum of IIC (odds ratio, 3.0; 95% confidence interval, 1.06-8.6; P = 0.03 for nonconvulsive status epilepticus-IIC). In addition, the suppression ratio was significantly negatively correlated with 2HELPS2B scores (Spearman coefficient = -0.37, P = 0.004 for left hemisphere and Spearman coefficient = -0.3, P = 0.02 for right hemisphere). Furthermore, patients with higher 2HELPS2B score (74% [14/19] in ≥2 points vs. 44% [14/32] in <2 points, P = 0.03 by χ 2 test) and lower suppression ratio (62% [23/37] in ≤2.18 vs. 35% [6/17] in >2.18, P = 0.06 by χ 2 test) seemed to be more responsive to subsequent anti-seizure drug., Conclusions: The 2HELPS2B score and background suppression can be used to distinguish the spectrum of IIC and thereby predict the response to subsequent anti-seizure drug., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 by the American Clinical Neurophysiology Society.)

The bidirectional association between primary esophageal squamous cell carcinoma (ESCC) and oral cavity squamous cell carcinoma (OSCC) suggests common risk factors and oncogenic molecular processes but it is unclear whether these two cancers display similar patterns of dysbiosis in their upper aerodigestive microbiota (UADM). We conducted a case-control study to characterize the microbial communities in esophageal lavage samples from 49 ESCC patients and oral rinse samples from 91 OSCC patients using 16S rRNA V3-V4 amplicon sequencing. Compared with their respective non-SCC controls from the same anatomical sites, 32 and 45 discriminative bacterial genera were detected in ESCC and OSCC patients, respectively. Interestingly, 20 of them were commonly enriched or depleted in both types of cancer, suggesting a convergent niche adaptation of upper aerodigestive SCC-associated bacteria that may play important roles in the pathogenesis of malignancies. Notably, Fusobacterium, Selenomonas, Peptoanaerobacter and Peptostreptococcus were enriched in both ESCC and OSCC, whereas Streptococcus and Granulicatelia were commonly depleted. We further identified Fusobacterium nucleatum as the most abundant species enriched in the upper aerodigestive SCC microenvironment, and the higher relative abundances of Selenomonas danae and Treponema maroon were positively correlated with smoking. In addition, predicted functional analysis revealed several depleted (eg, lipoic acid and pyruvate metabolism) and enriched (eg, RNA polymerase and nucleotide excision repair) pathways common to both cancers. Our findings reveal a convergent dysbiosis in the UADM between patients with ESCC and OSCC, suggesting a shared niche adaptation of host-microbiota interactions in the pathogenesis of upper aerodigestive tract malignancies., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Pre-vascularization has been receiving significant attention for developing implantable engineered 3D tissues. While various pre-vascularization techniques have been developed to improve graft vascularization, the effect of pre-vascularized patterns on in vivo neo-vessel formation has not been studied. In this study, we developed a functional pre-vascularized construct that significantly promotes graft vascularization and conducted in vivo evaluations of the micro-vascular patterns ( μ VPs) in various printed designs. μ VP formation, composed of high-density capillaries, was induced by the co-printing of endothelial cells and adipose-derived stem cells (ADSC). We implanted the printed constructs with various μ VP designs into a murine femoral arteriovenous bundle model and evaluated graft vascularization via 3D visualization and immune-histological analysis of the neo-vessels. The μ VP-distal group ( μ VP located away from the host vessel) showed approximately two-fold improved neo-vascularization compared to the μ VP-proximal group ( μ VP located near the host vessel). Additionally, we confirmed that the μ VP-distal group can generate the angiogenic factor gradient spatial environment for graft vascularization via computational simulations. Based on these results, the ADSC mono pattern (AMP), which secretes four times higher angiogenic factors than μ VP, was added to the μ VP + AMP group design. The μ VP + AMP group showed approximately 1.5- and 1.9-fold higher total sprouted neo-vessel volume than the μ VP only and AMP only groups, respectively. In immunohistochemical staining analysis, the μ VP + AMP group showed two-fold improved density and diameter of the matured neo-vessels. To summarize, these findings demonstrate graft vascularization accelerated due to design optimization of our pre-vascularized constructs. We believe that the developed pre-vascularization printing technique will facilitate new possibilities for the upscaling of implantable engineered tissues/organs., (© 2023 IOP Publishing Ltd.)

Achieving high mobility and bias stability is a challenging obstacle in the advancement of organic thin-film transistors (OTFTs). To this end, the fabrication of high-quality organic semiconductor (OSC) thin films is critical for OTFTs. Self-assembled monolayers (SAMs) have been used as growth templates for high-crystalline OSC thin films. Despite significant research progress in the growth of OSC on SAMs, a detailed understanding of the growth mechanism of the OSC thin films on a SAM template is lacking, which has limited its use. In this study, the effects of the structure (thickness and molecular packing) of SAM on the nucleation and growth behavior of the OSC thin films were investigated. We found that disordered SAM molecules assisted in the surface diffusion of the OSC molecules and resulted in a small nucleation density and large grain size of the OSC thin films. Moreover, a thick SAM with disordered SAM molecules on the top was found to be beneficial for the high mobility and bias stability of the OTFTs.

Despite the availability and use of numerous cholesterol-lowering drugs, atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality globally. Many researchers have focused their effort on identifying modified lipoproteins. However, lipid moieties such as lysophosphatidylcholine (LPC) and ceramide (CER) contribute to atherogenic events. LPC and CER both cause endothelial mitochondrial dysfunction, leading to fatty acid and triglyceride (TG) accumulation. In addition, they cause immune cells to differentiate into proinflammatory phenotypes. To uncover alternative therapeutic approaches other than cholesterol- and TG-lowering medications, we conducted untargeted lipidomic investigations to assess the alteration of lipid profiles in apolipoprotein E knockout ( apoE -/- ) mouse model, with or without feeding a high-fat diet (HFD). Results indicated that, in addition to hypercholesterolemia and hyperlipidemia, LPC levels were two to four times higher in apoE -/- mice compared to wild-type mice in C57BL/6 background, regardless of whether they were 8 or 16 weeks old. Sphingomyelin (SM) and CER were elevated three- to five-fold in apoE -/- mice both at the basal level and after 16 weeks when compared to wild-type mice. After HFD treatment, the difference in CER levels elevated more than ten-fold. Considering the atherogenic properties of LPC and CER, they may also contribute to the early onset of atherosclerosis in apoE -/- mice. In summary, the HFD-fed apoE -/- mouse shows elevated LPC and CER contents and is a suitable model for developing LPC- and CER-lowering therapies.

Phytochrome (Phy)-regulated light signalling plays important roles in plant growth, development, and stress responses. However, its function in rice defence against sheath blight disease (ShB) remains unclear. Here, we found that PhyB mutation or shade treatment promoted rice resistance to ShB, while resistance was reduced by PhyB overexpression. Further analysis showed that PhyB interacts with phytochrome-interacting factor-like 15 (PIL15), brassinazole resistant 1 (BZR1), and vascular plant one-zinc-finger 2 (VOZ2). Plants overexpressing PIL15 were more susceptible to ShB in contrast to bzr1-D-overexpressing plants compared with the wild-type, suggesting that PhyB may inhibit BZR1 to negatively regulate rice resistance to ShB. Although BZR1 is known to regulate brassinosteroid (BR) signalling, the observation that BR signalling negatively regulated resistance to ShB indicated an independent role for BZR1 in controlling rice resistance. It was also found that the BZR1 ligand NAC028 positively regulated resistance to ShB. RNA sequencing showed that cinnamyl alcohol dehydrogenase 8B (CAD8B), involved in lignin biosynthesis was upregulated in both bzr1-D- and NAC028-overexpressing plants compared with the wild-type. Yeast-one hybrid, ChIP, and transactivation assays demonstrated that BZR1 and NAC028 activate CAD8B directly. Taken together, the analyses demonstrated that PhyB-mediated light signalling inhibits the BZR1-NAC028-CAD8B pathway to regulate rice resistance to ShB., (© 2022 John Wiley & Sons Ltd.)

This study aimed to evaluate the alteration of PAP compliance after nasal surgery and to determine the optimal indications of nasal surgery in obstructive sleep apnea (OSA) subjects. Among OSA subjects using PAP devices, 29 subjects who underwent septoturbinoplasty due to nasal obstruction were included and their pre- and postoperative medical and PAP records were reviewed retrospectively. Postoperative autoPAP usage data was further assessed by grouping the compliance (the percentage of days with usage ≥ 4 h) data (group 1: the good compliance group; group 2: the poor compliance group). The data showed that 56% of subjects in group 1 complained of nasal obstruction as the only barrier to using a PAP device and about 89% reported experiencing the efficacy of PAP usage. Both the mean and peak average PAP pressures were significantly reduced in group 1 following nasal surgery. Group 2 had multiple subjective problems that interfered with wearing a PAP device and reported a lack of experiencing the efficacy of PAP usage. Preoperative nasal cavity volume values were smaller and absolute blood eosinophil counts were significantly lower in group 1. The current data demonstrate that nasal surgery might increase the compliance of PAP device wear in OSA subjects who complained of only nasal obstruction as a barrier to wearing PAP and who had small nasal cavity volumes combined with allergic inflammation., (© 2023. The Author(s).)

Cybersecurity is a growing concern in today's interconnected world. Traditional cybersecurity approaches, such as signature-based detection and rule-based firewalls, are often limited in their ability to effectively respond to evolving and sophisticated cyber threats. Reinforcement learning (RL) has shown great potential in solving complex decision-making problems in various domains, including cybersecurity. However, there are significant challenges to overcome, such as the lack of sufficient training data and the difficulty of modeling complex and dynamic attack scenarios hindering researchers' ability to address real-world challenges and advance the state of the art in RL cyber applications. In this work, we applied a deep RL (DRL) framework in adversarial cyber-attack simulation to enhance cybersecurity. Our framework uses an agent-based model to continuously learn from and adapt to the dynamic and uncertain environment of network security. The agent decides on the optimal attack actions to take based on the state of the network and the rewards it receives for its decisions. Our experiments on synthetic network security show that the DRL approach outperforms existing methods in terms of learning optimal attack actions. Our framework represents a promising step towards the development of more effective and dynamic cybersecurity solutions.