Fluorescent Chiral Quantum Dots to Unveil Origin-Dependent Exosome Uptake and Cargo Release.

Exosomes are promising nanocarriers for drug delivery. Yet, it is challenging to apply exosomes in clinical use due to the limited understanding of their physiological functions. While cellular uptake of exosomes is generally known through endocytosis and/or membrane fusion, the mechanisms of origin-dependent cellular uptake and subsequent cargo release of exosomes into recipient cells are still unclear. Herein, we investigated the intricate mechanisms of exosome entry into recipient cells and intracellular cargo release. In this study, we utilized chiral graphene quantum dots (GQDs) as representatives of exosomal cargo, taking advantage of the superior permeability of chiral GQDs into lipid membranes as well as their excellent optical properties for tracking analysis. We observed that the preferential cellular uptake of exosomes derived from the same cell-of-origin (intraspecies exosomes) is higher than that of exosomes derived from different cell-of-origin (cross-species exosomes). This uptake enhancement was attributed to receptor-ligand interaction-mediated endocytosis, as we identified the expression of specific ligands on exosomes that favorably interact with their parental cells and confirmed the higher lysosomal entrapment of intraspecies exosomes (intraspecies endocytic uptake). On the other hand, we found that the uptake of cross-species exosomes primarily occurred through membrane fusion, followed by direct cargo release into the cytosol (cross-species direct fusion uptake). We revealed the underlying mechanisms involved in the cellular uptake and subsequent cargo release of exosomes depending on their cell-of-origin and recipient cell types. Overall, this study envisions valuable insights into further advancements in effective drug delivery using exosomes, as well as a comprehensive understanding of cellular communication, including disease pathogenesis.

Lipidomics Analysis Unravels Aberrant Lipid Species and Pathways Induced by Zinc Oxide Nanoparticles in Kidney Cells.

Zinc oxide nanoparticles (ZnO NPs) are widely used in versatile applications, from high technology to household products. While numerous studies have examined the toxic gene profile of ZnO NPs across various tissues, the specific lipid species associated with adverse effects and potential biomarkers remain elusive. In this study, we conducted a liquid chromatography-mass spectrometry based lipidomics analysis to uncover potential lipid biomarkers in human kidney cells following treatment with ZnO NPs. Furthermore, we employed lipid pathway enrichment analysis (LIPEA) to elucidate altered lipid-related signaling pathways. Our results demonstrate that ZnO NPs induce cytotoxicity in renal epithelial cells and modulate lipid species; we identified 64 lipids with a fold change (FC) > 2 and p < 0.01 with corrected p < 0.05 in HK2 cells post-treatment with ZnO NPs. Notably, the altered lipids between control HK2 cells and those treated with ZnO NPs were associated with the sphingolipid, autophagy, and glycerophospholipid pathways. This study unveils novel potential lipid biomarkers of ZnO NP nanotoxicity, representing the first lipidomic profiling of ZnO NPs in human renal epithelial cells.

Stimulative piezoelectric nanofibrous scaffolds for enhanced small extracellular vesicle production in 3D cultures.

Small extracellular vesicles (sEVs) have great promise as effective carriers for drug delivery. However, the challenges associated with the efficient production of sEVs hinder their clinical applications. Herein, we report a stimulative 3D culture platform for enhanced sEV production. The proposed platform consists of a piezoelectric nanofibrous scaffold (PES) coupled with acoustic stimulation to enhance sEV production of cells in a 3D biomimetic microenvironment. Combining cell stimulation with a 3D culture platform in this stimulative PES enables a 49 fold increase in the production rate per cell with minimal deviations in particle size and protein composition compared with standard 2D cultures. We find that the enhanced sEV production is attributable to the activation and upregulation of crucial sEV production steps through the synergistic effect of stimulation and the 3D microenvironment. Moreover, changes in cell morphology lead to cytoskeleton redistribution through cell matrix interactions in the 3D cultures. This in turn facilitates intracellular EV trafficking, which impacts the production rate. Overall, our work provides a promising 3D cell culture platform based on piezoelectric biomaterials for enhanced sEV production. This platform is expected to accelerate the potential use of sEVs for drug delivery and broad biomedical applications.

Involvement of tumor necrosis factor receptor-associated factor 6 (TRAF6) in NF-κB activation and antiviral immunity: Molecular and functional characterization of TRAF6 in red-spotted grouper (Epinephelus akaara).

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a member of the TRAF family of adaptor proteins involved in the signal transduction pathways of both TNF receptor and interleukin-1 receptor/Toll-like receptor superfamilies. In this study, red-spotted grouper (Epinephelus akaara) TRAF6 (EaTraf6) was identified and characterized. The open reading frame of EaTraf6, 1713 bp in length, encodes a putative protein of 570 amino acids and has a predicted molecular weight and theoretical isoelectric point of 64.11 kDa and 6.07, respectively. EaTraf6 protein contains an N-terminal RING-type zinc finger domain, two TRAF-type zinc finger domains, a coiled-coil region (zf-TRAF), and a conserved C-terminal meprin and TRAF homology (MATH) domain. EaTraf6 shared the highest amino acid sequence identity with its ortholog from Epinephelus coioides, and phylogenetic analysis showed all fish TRAF6s clustered together and apart from other species. qRT-PCR results revealed that EaTraf6 was ubiquitously expressed in all examined tissues, with the highest level detected in the blood. In the immune challenge, EaTraf6 exhibited modulated mRNA expression levels in the blood and spleen. The subcellular localization analysis revealed that the EaTraf6 protein was predominantly present in the cytoplasm; however, it could translocate into the nucleus following poly (I:C) stimulation. The antiviral function of EaTraf6 was confirmed by analyzing the expression of host antiviral genes and viral genomic RNA during viral hemorrhagic septicemia virus infection. Additionally, luciferase reporter assay results indicated that EaTraf6 is involved in the activation of the NF-κB signaling pathway upon poly (I:C) stimulation. Finally, the effect of EaTraf6 on cytokine gene expression and its role in regulating macrophage M1 polarization were demonstrated. Collectively, these findings suggest that EaTraf6 is a crucial immune-related gene that significantly contributes to antiviral functions and regulation of NF-κB activity in the red-spotted grouper.

Motion correction of 3D dynamic contrast-enhanced ultrasound imaging without anatomical B-Mode images: Pilot evaluation in eight patients.

BACKGROUND: Dynamic contrast-enhanced ultrasound (DCE-US) is highly susceptible to motion artifacts arising from patient movement, respiration, and operator handling and experience. Motion artifacts can be especially problematic in the context of perfusion quantification. In conventional 2D DCE-US, motion correction (MC) algorithms take advantage of accompanying side-by-side anatomical B-Mode images that contain time-stable features. However, current commercial models of 3D DCE-US do not provide side-by-side B-Mode images, which makes MC challenging. PURPOSE: This work introduces a novel MC algorithm for 3D DCE-US and assesses its efficacy when handling clinical data sets. METHODS: In brief, the algorithm uses a pyramidal approach whereby short temporal windows consisting of three consecutive frames are created to perform local registrations, which are then registered to a master reference derived from a weighted average of all frames. We applied the algorithm to imaging studies from eight patients with metastatic lesions in the liver and assessed improvements in original versus motion corrected 3D DCE-US cine using: (i) frame-to-frame volumetric overlap of segmented lesions, (ii) normalized correlation coefficient (NCC) between frames (similarity analysis), and (iii) sum of squared errors (SSE), root-mean-squared error (RMSE), and r-squared (R2 ) quality-of-fit from fitted time-intensity curves (TIC) extracted from a segmented lesion. RESULTS: We noted improvements in frame-to-frame lesion overlap across all patients, from 68% ± 13% without correction to 83% ± 3% with MC (p = 0.023). Frame-to-frame similarity as assessed by NCC also improved on two different sets of time points from 0.694 ± 0.057 (original cine) to 0.862 ± 0.049 (corresponding MC cine) and 0.723 ± 0.066 to 0.886 ± 0.036 (p ≤ 0.001 for both). TIC analysis displayed a significant decrease in RMSE (p = 0.018) and a significant increase in R2 goodness-of-fit (p = 0.029) for the patient cohort. CONCLUSIONS: Overall, results suggest decreases in 3D DCE-US motion after applying the proposed algorithm.

Modulation of Cisplatin Sensitivity through TRPML1-Mediated Lysosomal Exocytosis in Ovarian Cancer Cells: A Comprehensive Metabolomic Approach.

BACKGROUND: The lysosome has emerged as a promising target for overcoming chemoresistance, owing to its role in facilitating the lysosomal sequestration of drugs. The lysosomal calcium channel TRPML1 not only influences lysosomal biogenesis but also coordinates both endocytosis and exocytosis. This study explored the modulation of cisplatin sensitivity by regulating TRPML1-mediated lysosomal exocytosis and identified the metabolomic profile altered by TRPML1 inhibition. METHODS: We used four types of ovarian cancer cells: two cancer cell lines (OVCAR8 and TOV21G) and two patient-derived ovarian cancer cells. Metabolomic analyses were conducted to identify altered metabolites by TRPML1 inhibition. RESULTS: Lysosomal exocytosis in response to cisplatin was observed in resistant cancer cells, whereas the phenomenon was absent in sensitive cancer cells. Through the pharmacological intervention of TRPML1, lysosomal exocytosis was interrupted, leading to the sensitization of resistant cancer cells to cisplatin treatment. To assess the impact of lysosomal exocytosis on chemoresistance, we conducted an untargeted metabolomic analysis on cisplatin-resistant ovarian cancer cells with TRPML1 inhibition. Among the 1446 differentially identified metabolites, we focused on 84 significant metabolites. Metabolite set analysis revealed their involvement in diverse pathways. CONCLUSIONS: These findings collectively have the potential to enhance our understanding of the interplay between lysosomal exocytosis and chemoresistance, providing valuable insights for the development of innovative therapeutic strategies.

Type 2 diabetes and its genetic susceptibility are associated with increased severity and mortality of COVID-19 in UK Biobank.

Type 2 diabetes (T2D) is known as one of the important risk factors for the severity and mortality of COVID-19. Here, we evaluate the impact of T2D and its genetic susceptibility on the severity and mortality of COVID-19, using 459,119 individuals in UK Biobank. Utilizing the polygenic risk scores (PRS) for T2D, we identified a significant association between T2D or T2D PRS, and COVID-19 severity. We further discovered the efficacy of vaccination and the pivotal role of T2D-related genetics in the pathogenesis of severe COVID-19. Moreover, we found that individuals with T2D or those in the high T2D PRS group had a significantly increased mortality rate. We also observed that the mortality rate for SARS-CoV-2-infected patients was approximately 2 to 7 times higher than for those not infected, depending on the time of infection. These findings emphasize the potential of T2D PRS in estimating the severity and mortality of COVID-19.

Brain Mapping Using a Graphene Electrode Array.

Cortical maps represent the spatial organization of location-dependent neural responses to sensorimotor stimuli in the cerebral cortex, enabling the prediction of physiologically relevant behaviors. Various methods, such as penetrating electrodes, electroencephalography, positron emission tomography, magnetoencephalography, and functional magnetic resonance imaging, have been used to obtain cortical maps. However, these methods are limited by poor spatiotemporal resolution, low signal-to-noise ratio (SNR), high costs, and non-biocompatibility or cause physical damage to the brain. This study proposes a graphene array-based somatosensory mapping method as a feature of electrocorticography that offers superior biocompatibility, high spatiotemporal resolution, desirable SNR, and minimized tissue damage, overcoming the drawbacks of previous methods. This study demonstrated the feasibility of a graphene electrode array for somatosensory mapping in rats. The presented protocol can be applied not only to the somatosensory cortex but also to other cortices such as the auditory, visual, and motor cortex, providing advanced technology for clinical implementation.

Galectin 9 restricts viral replication in teleost via autophagy-antiviral pathway and polarizes M2 macrophages for anti-inflammatory response: New insights into functional properties of fish Galectin-9 from Planiliza haematocheilus.

Galectin 9 (Gal9) is a tandem repeat type ß-galactoside-binding galectin that mediates various cellular biochemical and immunological functions. Many studies have investigated the functional properties of Gal9 in mammals; however, knowledge of fish Gal9 is limited to antibacterial studies. In this context, our aim was to clone Gal9 from Planiliza haematocheilus (PhGal9) and investigate its structural and functional characteristics. We discovered the PhGal9 open reading frame, which was 969 base pairs long and encoded a 322 amino acid protein. PhGal9 had a projected molecular weight of 35.385 kDa but no signal peptide sequence. PhGal9 mRNA was ubiquitously produced in all investigated tissues but was predominant in the intestine, spleen, and brain. Its mRNA expression was increased in response to stimulation by Poly(I:C), LPS, and L. garvieae. The rPhGal9 exhibited a dose-dependent agglutination potential toward gram-positive and gram-negative bacteria at a minimum concentration of 50 µg/mL. Overexpression of PhGal9 promoted M2-like phenotype changes in mouse macrophages, and RT-qPCR analysis of M1 and M2 marker genes confirmed M2 polarization with upregulation of M2 marker genes. In the antiviral assay, the expression levels of Viral Hemorrhagic Septicemia Virus (VHSV) glycoproteins, phosphoproteins, nucleoproteins, non-virion proteins, matrix proteins, and RNA polymerase were significantly reduced in PhGal9-overexpressed cells. Furthermore, the mRNA expression of autophagic genes (sqstm1, tax1bp1b, rnf13, lc3, and atg5) and antiviral genes (viperin) were upregulated in PhGal9 overexpressed cells. For the first time in teleosts, our study demonstrated that PhGal9 promotes M2 macrophage polarization by upregulating M2-associated genes (egr2 and cmyc) and suppressing M1-associated genes (iNOS and IL-6). Furthermore, our results show that exogenous and endogenous PhGal9 prevented VHSV attachment and replication by neutralizing virion and autophagy, respectively. Gal9 may be a potent modulator of the antimicrobial immune response in teleost fish.

ABA-dependent suberization and aquaporin activity in rice (Oryza sativa L.) root under different water potentials.

Drought is one of the most stressful environments limiting crop growth and yield throughout the world. Therefore, most efforts have been made to document drought-derived genetic and physiological responses and to find better ways to improve drought tolerance. The interaction among them is unclear and/or less investigated. Therefore, the current study is to find a clue of metabolic connectivity among them in rice root experiencing different levels of drought condition. We selected 19 genes directly involved in abscisic acid (ABA) metabolism (6), suberization (6), and aquaporins (AQPs) activity (7) and analyzed the relatively quantitative gene expression using qRT-PCR from rice roots. In addition, we also analyzed proline, chlorophyll, and fatty acids and observed cross-sectional root structure (aerenchyma) and suberin lamella deposition in the endodermis. All drought conditions resulted in an obvious development of aerenchyma and two- to fourfold greater accumulation of proline. The limited water supply (-1.0 and -1.5 MPa) significantly increased gene expression (ABA metabolism, suberization, and AQPs) and developed greater layer of suberin lamella in root endodermis. In addition, the ratio of the unsaturated to the saturated fatty acids was increased, which could be considered as an adjusted cell permeability. Interestingly, these metabolic adaptations were an exception with a severe drought condition (hygroscopic coefficient, -3.1 MPa). Accordingly, we concluded that the drought-tolerant mechanism in rice roots is sophisticatedly regulated until permanent wilting point (-1.5 MPa), and ABA metabolism, suberization, and AQPs activity might be independent and/or concurrent process as a survival strategy against drought.

Chirality-enhanced transport and drug delivery of graphene nanocarriers to tumor-like cellular spheroid.

Chirality, defined as "a mirror image," is a universal geometry of biological and nonbiological forms of matter. This geometry of molecules determines how they interact during their assembly and transport. With the development of nanotechnology, many nanoparticles with chiral geometry or chiroptical activity have emerged for biomedical research. The mechanisms by which chirality originates and the corresponding synthesis methods have been discussed and developed in the past decade. Inspired by the chiral selectivity in life, a comprehensive and in-depth study of interactions between chiral nanomaterials and biological systems has far-reaching significance in biomedicine. Here, we investigated the effect of the chirality of nanoscale drug carriers, graphene quantum dots (GQDs), on their transport in tumor-like cellular spheroids. Chirality of GQDs (L/D-GQDs) was achieved by the surface modification of GQDs with L/D-cysteines. As an in-vitro tissue model for drug testing, cellular spheroids were derived from a human hepatoma cell line (i.e., HepG2 cells) using the Hanging-drop method. Our results reveal that the L-GQDs had a 1.7-fold higher apparent diffusion coefficient than the D-GQDs, indicating that the L-GQDs can enhance their transport into tumor-like cellular spheroids. Moreover, when loaded with a common chemotherapy drug, Doxorubicin (DOX), via π-π stacking, L-GQDs are more effective as nanocarriers for drug delivery into solid tumor-like tissue, resulting in 25% higher efficacy for cancerous cellular spheroids than free DOX. Overall, our studies indicated that the chirality of nanocarriers is essential for the design of drug delivery vehicles to enhance the transport of drugs in a cancerous tumor.

Radiologic Follow-up of Ruptured Arachnoid Cysts With or Without Hemorrhage: Five Case Reports and a Review of the Literature.

Arachnoid cysts are usually asymptomatic and discovered incidentally. However, cysts may occasionally rupture because of minor head trauma. We describe the radiologic follow-up of 5 patients with ruptured arachnoid cysts featuring spontaneous resolution, subdural hygroma formation, and cystic and subdural hemorrhage. From January 2004 through July 2020, 5 patients (1.3%) with ruptured arachnoid cysts were evaluated out of 388 patients with arachnoid cysts encountered at our institution at that time. The 5 patients were all male, and they ranged in age from 6-17 years (median, 12 years). The median duration of radiologic follow-up was 3.5 years (range, 2.3-10.1 years). All of the ruptured arachnoid cysts were overlying the temporal lobe with Galassi type II. The median cyst diameter was 4.9 cm (range, 4.4-8.9 cm). Four patients had a history of recent minor head trauma. There were no particular neurologic symptoms in their past medical history in all patients. In the follow-up, two patients' cysts resolved spontaneously without hemorrhage. One patient's cyst resolved post-burr-hole drainage for chronic subdural hemorrhage. Another patient, whose cyst led to a hemorrhage and chronic subdural hemorrhage, recovered following a craniotomy, hematoma removal, and cyst fenestration. Another patient, presenting with hygroma, cystic hemorrhage, and chronic subdural hemorrhage, was treated with burr-hole drainage. Three patients recovered postoperatively. Arachnoid cysts rarely rupture, and surgical intervention is required for some cases associated with hemorrhage. Postoperatively, all patients had good outcomes without complications in this series.

Zinc oxide nanoparticles trigger autophagy-mediated cell death through activating lysosomal TRPML1 in normal kidney cells.

Zinc oxide nanoparticles (ZnO NPs) have been widely used in various materials including sunscreens, cosmetics, over-the-counter topical skin products, and pigments. As traces of the used ZnO NPs have been found in the kidney, it is crucial to uncover their potential risks. The aim of this study is to elucidate detrimental effects of ZnO NPs and the molecular mechanism behind their renal toxicity. Cytotoxic effects were measured by MTT assay after HK2 cells were exposed to ZnO NPs for 24 h and IC50 value was determined. ROS and intracellular Zn2+ levels were detected by flow cytometry, and localization of Zn2+ and lysosome was determined by confocal microscopy. Occurrence of autophagy and detection of autophagic flux were determined by Western blot and confocal microscopy, respectively. We performed unpaired student t test for two groups, and one-way ANOVA with Tukey's post hoc for over three groups. ZnO NPs induced cell death in human renal proximal tubule epithelial cells, HK2. Cytosolic Zn2+ caused autophagy-mediated cell death rather than apoptosis. Cytosolic Zn2+ processed in lysosome was released by TRPML1, and inhibition of TRPML1 significantly decreased autophagic flux and cell death. The findings of this study suggest that ZnO NPs strongly induce autophagy-mediated cell death in human kidney cells. Controlling TRPML1 can be potentially used to prevent the kidney from ZnO NPs-induced toxicity.

Effects of Health Education Using Virtual Reality for Adolescents: A Systematic Review and Meta-Analysis.

PURPOSE: This study aimed to evaluate the effects of health interventions using virtual reality (VR) on improving knowledge, attitudes, and skills; and inducing behavioral change among adolescents. METHODS: This study is a systematic review and meta-analysis following PRISMA guidelines. We searched Cochrane, MEDLINE, Embase, CINAHL, Scopus, Web of Science, and Korean databases between database inception and April 10, 2021. Based on heterogeneity, a random- or fixed-effects model was used, as appropriate, to calculate effect sizes in terms of the standardized mean difference (SMD) and odds ratio (OR). Studies were selected if they verified the effects of health education using VR on adolescents; there was an appropriate control group; and if the effects of education were reported in terms of changes in knowledge, attitudes, skills, or behaviors. RESULTS: This analysis included six studies (n = 1,086). The intervention groups showed greater responses in knowledge and attitudes (SMD = 0.57, 95% confidence interval (CI) [0.12 to 1.02]), skills related to health behavior (SMD = -0.45, 95% CI [-0.71 to -0.19]), and behavioral change after 12 months (OR = 2.36, 95% CI [1.03 to 5.41]). CONCLUSION: The results confirm the effectiveness of health interventions using virtual reality (VR). Although the analysis include a small number of studies, a case can be made for health interventions using VR to be utilized as educational methods and strategies to prevent risky behaviors among adolescents.

Chiral Graphene Quantum Dots Enhanced Drug Loading into Small Extracellular Vesicles.

As nanoscale extracellular vesicles secreted by cells, small extracellular vesicles (sEVs) have enormous potential as safe and effective vehicles to deliver drugs into lesion locations. Despite promising advances with sEV-based drug delivery systems, there are still challenges to drug loading into sEVs, which hinder the clinical applications of sEVs. Herein, we report an exogenous drug-agnostic chiral graphene quantum dots (GQDs) sEV-loading platform, based on chirality matching with the sEV lipid bilayer. Both hydrophobic and hydrophilic chemical and biological drugs can be functionalized or adsorbed onto GQDs by π-π stacking and van der Waals interactions. By tuning the ligands and GQD size to optimize its chirality, we demonstrate drug loading efficiency of 66.3% and 64.1% for doxorubicin and siRNA, which is significantly higher than other reported sEV loading techniques.

Identification, expression profiling, and functional characterization of cystatin C from big-belly seahorse (Hippocampus abdominalis).

Cystatins are natural inhibitors of lysosomal cysteine proteases, including cathepsins B, L, H, and S. Cystatin C (CSTC) is a member of the type 2 cystatin family and is an essential biomarker in the prognosis of several diseases. Emerging evidence suggests the immune regulatory roles of CSTC in antigen presentation, the release of different inflammatory mediators, and apoptosis in various pathophysiologies. In this study, the 390-bp cystatin C (HaCSTC) cDNA from big-belly seahorse (Hippocampus abdominalis) was cloned and characterized by screening the pre-established cDNA library. Based on similarities in sequence, HaCSTC is a homolog of the teleost type 2 cystatin family with putative catalytic cystatin domains, signal peptides, and disulfide bonds. HaCSTC transcripts were ubiquitously expressed in all tested big-belly seahorse tissues, with the highest expression in ovaries. Immune challenge with lipopolysaccharides, polyinosinic:polycytidylic acid, Edwardsiella tarda, and Streptococcus iniae caused significant upregulation in HaCSTC transcript levels. Using a pMAL-c5X expression vector, the 14.29-kDa protein of recombinant HaCSTC (rHaCSTC) was expressed in Escherichia coli BL21 (DE3), and its protease inhibitory activity against papain cysteine protease was determined with the aid of a protease substrate. Papain was competitively blocked by rHaCSTC in a dose-dependent manner. In response to viral hemorrhagic septicemia virus (VHSV) infection, HaCSTC overexpression strongly decreased the expression of VHSV transcripts, pro-inflammatory cytokines, and pro-apoptotic genes; while increasing the expression of anti-apoptotic genes in fathead minnow (FHM) cells. Furthermore, HaCSTC overexpression protected VHSV-infected FHM cells against VHSV-induced apoptosis and increased cell viability. Our findings imply the profound role of HaCSTC against pathogen infections by modulating fish immune responses.

Understanding the Effect of Side Reactions on the Recyclability of Furan-Maleimide Resins Based on Thermoreversible Diels-Alder Network.

We studied the effect of side reactions on the reversibility of epoxy with thermoreversible Diels-Alder (DA) cycloadducts based on furan and maleimide chemistry. The most common side reaction is the maleimide homopolymerization which introduces irreversible crosslinking in the network adversely affecting the recyclability. The main challenge is that the temperatures at which maleimide homopolymerization can occur are approximately the same as the temperatures at which retro-DA (rDA) reactions depolymerize the networks. Here we conducted detailed studies on three different strategies to minimize the effect of the side reaction. First, we controlled the ratio of maleimide to furan to reduce the concentration of maleimide groups which diminishes the effects of the side reaction. Second, we applied a radical-reaction inhibitor. Inclusion of hydroquinone, a known free radical scavenger, is found to retard the onset of the side reaction both in the temperature sweep and isothermal measurements. Finally, we employed a new trismaleimide precursor that has a lower maleimide concentration and reduces the rate of the side reaction. Our results provide insights into how to minimize formation of irreversible crosslinking by side reactions in reversible DA materials using maleimides, which is important for their application as novel self-healing, recyclable, and 3D-printable materials.

Early-Onset Insomnia among Patients with Hemifacial Spasm in South Korea: A Nationwide Cohort Study.

This study aimed to investigate mental illnesses among patients with hemifacial spasms (HFS) based on nationwide claims data from the South Korea Health Insurance Review and Assessment Service. In this retrospective study, we defined the HFS group as subjects aged between 20 and 79 years with newly diagnosed HFS between January 2011 and December 2019 and set the date of diagnosis of HFS as the index date. Mental illnesses were defined through the International Classification of Diseases, the tenth revision from 90 days before to after the index date. Of these patients, we enrolled the participants who had visited a psychiatric outpatient clinic more than twice or had been admitted to a psychiatric department more than once diagnosed with psychiatric diseases. To select the control group, which was four times larger than the HFS group, propensity scores were used among those not diagnosed with HFS. The patients with HFS were more likely to have a mental illness than the control group (8.5% and 6.5%, respectively, p < 0.001) within 90 days before and after diagnosis. Among mental illnesses, insomnia (46.2% vs. 13.0%, p < 0.001) was significantly more prevalent in the HFS group. Other mental illnesses were significantly more prevalent in the control group or were not statistically significant. The results of this study suggest that patients diagnosed with HFS were significantly more likely to develop insomnia within a relatively short period than the controls.

Understanding the Impact of the COVID-19 Pandemic on the Perception and Use of Urban Green Spaces in Korea.

Faced with the prospect that the impact of the COVID-19 pandemic and climate change will be far-reaching and long-term, the international community is showing interest in urban green space (UGS) and urban green infrastructure utilization as a solution. In this study, we investigated how citizens' perceptions and use of UGS have changed during COVID-19. We also collected their ideas on how UGS can raise its usability. As a result, more people became to realize the importance of UGS. In particular, the urban environmental purification function from UGS was recognized as giving great benefits to respondents. On the other hand, the patterns of UGS use were mixed with decreasing UGS use to maintain social distancing or increasing UGS use to maintain health or substitute other restricted facilities. More than half of respondents had their UGS visit patterns impacted by COVID-19. In particular, the increase rate of UGS use was rather high in the group that seldom used UGS before COVID-19. In addition, they increased the use of UGS to replace other limited facilities, and thus tended to demand an increase in rest facilities. Based on these results, this paper suggested securing social support and sustainability for the policy by reflecting users' demand in landscape planning related to the increase of UGS in the city. This study can contribute to improving the resilience of UGS and the sustainability of urban space planning.