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Abstract Van der Waals (vdW) stacking is a powerful technique to achieve desired properties in condensed matter systems through layer-by-layer crystal engineering. A remarkable example is the control over the twist angle between artificially-stacked vdW crystals, enabling the realization of unconventional phenomena in moiré structures ranging from superconductivity to strongly correlated magnetism. Here, we report the appearance of unusual 120° twisted faults in vdW magnet CrI3 crystals. In exfoliated samples, we observe vertical twisted domains with a thickness below 10 nm. The size and distribution of twisted domains strongly depend on the sample preparation methods, with as-synthesized unexfoliated samples showing tenfold thicker domains than exfoliated samples. Cooling induces changes in the relative populations among different twisting domains, rather than the previously assumed structural phase transition to the rhombohedral stacking. The stacking disorder induced by sample fabrication processes may explain the unresolved thickness-dependent magnetic coupling observed in CrI3.

Abstract Mixed-dimensional van der Waals (vdW) heterostructures offer promising platforms for exploring interesting phenomena and functionalities. To exploit their full potential, precise epitaxial processes and well-defined heterointerfaces between different components are essential. Here, we control the growth of one-dimensional (1D) vdW microwires on hexagonal crystals via plasma treatment of the growth templates. AgCN serves as a model 1D system for examining the dependence of the nucleation and growth parameters on the surface treatment conditions and substrate types. The oxygen-plasma-treated transition metal dichalcogenides form step edges mediated by formation of surface metal oxides, leading to robust AgCN epitaxy with an enhanced nucleation density and low horizontal growth rates. Monte Carlo simulations reproduce the experimentally observed growth behaviors and unveil the crucial growth parameters, such as surface diffusivity. The plasma treatment results in distinct effects on graphite and hexagonal boron nitride templates, which undergo plasma-induced amorphization and deactivation of the AgCN vdW epitaxy. We achieve the selective growth of AgCN microwires on graphite using the deactivated vdW epitaxy. This study offers significant insights into the impact of surface treatment on 1D vdW epitaxy, opening avenues for controlled fabrication of mixed-dimensional vdW heterostructures.

Abstract Background Convolutional neural network-based image processing research is actively being conducted for pathology image analysis. As a convolutional neural network model requires a large amount of image data for training, active learning (AL) has been developed to produce efficient learning with a small amount of training data. However, existing studies have not specifically considered the characteristics of pathological data collected from the workplace. For various reasons, noisy patches can be selected instead of clean patches during AL, thereby reducing its efficiency. This study proposes an effective AL method for cancer pathology that works robustly on noisy datasets. Methods Our proposed method to develop a robust AL approach for noisy histopathology datasets consists of the following three steps: 1) training a loss prediction module, 2) collecting predicted loss values, and 3) sampling data for labeling. This proposed method calculates the amount of information in unlabeled data as predicted loss values and removes noisy data based on predicted loss values to reduce the rate at which noisy data are selected from the unlabeled dataset. We identified a suitable threshold for optimizing the efficiency of AL through sensitivity analysis. Results We compared the results obtained with the identified threshold with those of existing representative AL methods. In the final iteration, the proposed method achieved a performance of 91.7% on the noisy dataset and 92.4% on the clean dataset, resulting in a performance reduction of less than 1%. Concomitantly, the noise selection ratio averaged only 2.93% on each iteration. Conclusions The proposed AL method showed robust performance on datasets containing noisy data by avoiding data selection in predictive loss intervals where noisy data are likely to be distributed. The proposed method contributes to medical image analysis by screening data and producing a robust and effective classification model tailored for cancer pathology image processing in the workplace.

Abstract Although uric acid-lowering agents such as xanthine oxidase inhibitors have potential cardioprotective effects, studies on their use in preventing cardiovascular diseases are lacking. We investigated the genetically proxied effects of reducing uric acid on ischemic cardiovascular diseases in a lipid-level-stratified population. We performed drug-target Mendelian randomization (MR) analyses using UK Biobank data to select genetic instruments within a uric acid-lowering gene, xanthine dehydrogenase (XDH), and construct genetic scores. For nonlinear MR analyses, individuals were stratified by lipid level. Outcomes included acute myocardial infarction (AMI), ischemic heart disease, cerebral infarction, transient cerebral ischemic attack, overall ischemic disease, and gout. We included 474,983 non-gout individuals with XDH-associated single-nucleotide polymorphisms. The XDH-variant-induced uric acid reduction was associated with reduced risk of gout (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.78–0.93; P

Summary: Background: The current pipeline for new antibiotics fails to fully address the significant threat posed by drug-resistant Gram-negative bacteria that have been identified by the World Health Organization (WHO) as a global health priority. New antibacterials acting through novel mechanisms of action are urgently needed. We aimed to identify new chemical entities (NCEs) with activity against Klebsiella pneumoniae and Acinetobacter baumannii that could be developed into a new treatment for drug-resistant infections. Methods: We developed a high-throughput phenotypic screen and selection cascade for generation of hit compounds active against multidrug-resistant (MDR) strains of K. pneumoniae and A. baumannii. We screened compound libraries selected from the proprietary collections of three pharmaceutical companies that had exited antibacterial drug discovery but continued to accumulate new compounds to their collection. Compounds from two out of three libraries were selected using “eNTRy rules” criteria associated with increased likelihood of intracellular accumulation in Escherichia coli. Findings: We identified 72 compounds with confirmed activity against K. pneumoniae and/or drug-resistant A. baumannii. Two new chemical series with activity against XDR A. baumannii were identified meeting our criteria of potency (EC50 ≤50 μM) and absence of cytotoxicity (HepG2 CC50 ≥100 μM and red blood cell lysis HC50 ≥100 μM). The activity of close analogues of the two chemical series was also determined against A. baumannii clinical isolates. Interpretation: This work provides proof of principle for the screening strategy developed to identify NCEs with antibacterial activity against multidrug-resistant critical priority pathogens such as K. pneumoniae and A. baumannii. The screening and hit selection cascade established here provide an excellent foundation for further screening of new compound libraries to identify high quality starting points for new antibacterial lead generation projects. Funding: BMBF and GARDP.

Abstract Understanding the nature of molecular excitons in low-dimensional molecular solids is of paramount importance in fundamental photophysics and various applications such as energy harvesting, switching electronics and display devices. Despite this, the spatial evolution of molecular excitons and their transition dipoles have not been captured in the precision of molecular length scales. Here we show in-plane and out-of-plane excitonic evolution in quasilayered two-dimensional (2D) perylene-3, 4, 9, 10-tetracarboxylic dianhydride (PTCDA) crystals assembly-grown on hexagonal boron nitride (hBN) crystals. Complete lattice constants with orientations of two herringbone-configured basis molecules are determined with polarization-resolved spectroscopy and electron diffraction methods. In the truly 2D limit of single layers, two Frenkel emissions Davydov-split by Kasha-type intralayer coupling exhibit energy inversion with decreasing temperature, which enhances excitonic coherence. As the thickness increases, the transition dipole moments of newly emerging charge transfer excitons are reoriented because of mixing with the Frenkel states. The current spatial anatomy of 2D molecular excitons will inspire a deeper understanding and groundbreaking applications of low-dimensional molecular systems.

2D layered materials attract interest due to their potential for application in nanoelectronics and optoelectronics. Here authors report an order-disorder-type phase transition driven by temperature in bulk lead iodides, and interlayer sliding is identified to play a key role in the mechanism of this phase transition.

Abstract BackgroundDigital health technologies are widely used for disease management, with their computing platforms, software, and sensors being used for health care. These technologies are developed to manage chronic diseases and infectious bacterial diseases, including tuberculosis (TB). ObjectiveThis study aims to comprehensively review the literature on the use of digital health interventions (DHIs) for enhancing TB treatment adherence and identify major strategies for their adoption. MethodsWe conducted a literature search in the PubMed, Cochrane Library, Ovid Embase, and Scopus databases for relevant studies published between January 2012 and March 2022. Studies that focused on web-based or mobile phone–based interventions, medication adherence, digital health, randomized controlled trials, digital interventions, or mobile health and ubiquitous health technology for TB treatment and related health outcomes were included. ResultsWe identified 27 relevant studies and classified them according to the intervention method, a significant difference in treatment success, and health outcomes. The following interventions were emphasized: SMS text messaging interventions (8/27, 30%), medicine reminders (6/27, 22%), and web-based direct observation therapy (9/27, 33%). Digital health technology significantly promoted disease management among individuals and health care professionals. However, only a few studies addressed 2-way communication therapies, such as interactive SMS text messaging and feedback systems. ConclusionsThis scoping review classified studies on DHIs for patients with TB and demonstrated their potential for the self-management of TB. DHIs are still being developed, and evidence on the impact of digital technologies on enhancing TB treatment adherence remains limited. However, it is necessary to encourage patients’ participation in TB treatment and self-management through bidirectional communication. We emphasize the importance of developing a communication system.

Canonical helical antimicrobial peptides are less insertive and less active. Here, an improved antimicrobial peptide, WCopWs, indicate that matching amino acids membrane preference profile improves insertion and activity.

Sargassum horneri (S. horneri) is a brown seaweed that contains a fucose-rich sulfated polysaccharide called fucoidan and is known to possess beneficial bioactivities, such as anti-inflammatory, antiviral, antioxidative, and antitumoral effects. This study aimed to determine the anti-inflammatory effects of AB_SH (hydrothermal extracts from S. horneri) and its bioactive compound (fucoidan) against tumor necrosis factor alpha (TNF-α)-induced inflammation in human retinal pigment epithelial (RPE) cells. AB_SH did not exhibit any cytotoxicity, and it decreased the mRNA expression of interleukin (IL)-6 and IL-8 and the production of the cytokines IL-6 and TNF-α. It also suppressed the expression levels of phosphorylated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs), including c-Jun amino-terminal kinases (JNK), p38 protein kinases (p38), and extracellular signal-regulated kinase (ERK) proteins, suggesting that AB_SH inhibits activation of the NF-kB/MAPK signaling pathway. Since fucoidan was identified in the composition analysis of AB_SH, it was additionally shown to be required for its anti-inflammatory effects in TNF-α-stimulated human RPE cells. In line with the AB_SH results, fucoidan reduced the mRNA levels of IL-6, IL-1ß, and IL-8 and production of the cytokines IL-6, TNF-α, and IL-8 through the downregulation of the NF-kB/MAPK signaling pathway in a dose-dependent manner. Collectively, the ability of AB_SH from S. horneri hydrothermal extracts to reduce inflammation indicates that it may be a good functional ingredient for managing ocular disorders.

Owing to increasing air pollution due to industrial development, fine dust has been associated with threatening public health. In particular, ultrafine urban particulate matter (uf-UP, PM 0.1) can easily enter our bodies, causing inflammation-related diseases. Therefore, in the present study, we evaluated the effects of hydrothermal extracts of Sargassum horneri and its bioactive compound, loliolide, on uf-UP-induced inflammation as a potential treatment strategy for retinal disorders. Human retinal pigment epithelial cells (ARPE-19) stimulated with TNF-α or uf-UPs were treated with S. horneri extract and loliolide. S. horneri extracts exhibited anti-inflammatory effects on uf-UP-induced inflammation without cell toxicity through downregulating the mRNA expression of MCP-1, IL-8, IL-6, and TNF-α. UPLC-QTOF/MS analysis confirmed that the hydrothermal extract of S. horneri contained loliolide, which has anti-inflammatory effects. Loliolide effectively reduced the mRNA expression and production of proinflammatory chemokines (IL-8) and cytokines (IL-1β and IL-6) by downregulating the MAPK/NF-ĸB signaling pathway on TNF-α-stimulated inflammatory ARPE-19 cells. These effects were further confirmed in inflammatory ARPE-19 cells after stimulation with uf-UPs. Collectively, these results suggested the application of S. horneri as a functional ingredient for treating ocular disorders caused by particular matters.

Abstract We study a low voltage short pulse operating multilevel memory based on van der Waals heterostack (HS) n-MoSe2/n-MoS2 channel field-effect transistors (FETs). Our HS memory FET exploited the gate voltage (VGS)-induced trapping/de-trapping phenomena for Program/Erase functioning, which was maintained for long retention times owing to the existence of heterojunction energy barrier between MoS2 and MoSe2. More interestingly, trapped electron density was incrementally modulated by the magnitude or cycles of a pulsed VGS, enabling the HS device to achieve multilevel long-term memory. For a practical demonstration, five different levels of drain current were visualized with multiscale light emissions after our memory FET was integrated into an organic light-emitting diode pixel circuit. In addition, our device was applied to a synapse-imitating neuromorphic memory in an artificial neural network. We regard our unique HS channel FET to be an interesting and promising electron device undertaking multifunctional operations related to the upcoming fourth industrial revolution era.

Abstract Background COVID-19, caused by SARS-CoV-2 has become the most threatening issue to all populations around the world. It is, directly and indirectly, affecting all of us and thus, is an emerging topic dealt in global health. To avoid the infection, various studies have been done and are still ongoing. COVID-19 cases are reported all over the globe, and among the millions of cases, genetic similarity may be seen. The genetical common features seen within confirmed cases may help outline the tendency of infection and degree severity of the disease. Here, we reviewed multiple papers on SNPs related to SARS-CoV-2 infection and analyzed their results. Methods The PubMed databases were searched for papers discussing SNPs associated with SARS-CoV-2 infection and severity. Clinical studies with human patients and statistically showing the relevance of the SNP with virus infection were included. Quality Assessment of all papers was done with Newcastle Ottawa Scale. Results In the analysis, 21 full-text literature out of 2956 screened titles and abstracts, including 63,496 cases, were included. All were human-based clinical studies, some based on certain regions gathered patient data and some based on big databases obtained online. ACE2, TMPRSS2, and IFITM3 are the genes mentioned most frequently that are related to SARS-CoV-2 infection. 20 out of 21 studies mentioned one or more of those genes. The relevant genes according to SNPs were also analyzed. rs12252-C, rs143936283, rs2285666, rs41303171, and rs35803318 are the SNPs that were mentioned at least twice in two different studies. Conclusions We found that ACE2, TMPRSS2, and IFITM3 are the major genes that are involved in SARS-CoV-2 infection. The mentioned SNPs were all related to one or more of the above-mentioned genes. There were discussions on certain SNPs that increased the infection and severity to certain groups more than the others. However, as there is limited follow-up and data due to a shortage of time history of the disease, studies may be limited.

This paper proposes an algorithm for transmitting and reconstructing the estimated point cloud by temporally estimating a dynamic point cloud sequence. When a non-rigid 3D point cloud sequence (PCS) is input, the sequence is divided into groups of point cloud frames (PCFs), and a key PCF is selected. The 3D skeleton is predicted through 3D pose estimation, and the motion of the skeleton is estimated by analyzing the joints and bones of the 3D skeleton. For the deformation of the non-rigid human PC, the 3D PC model is transformed into a mesh model, and the key PCF is rigged using the 3D skeleton. After deforming the key PCF into the target PCF utilizing the motion vector of the estimated skeleton, the residual PC between the motion compensation PCF and the target PCF is generated. If there is a key PCF, the motion vector of the target PCF, and a residual PC, the target PCF can be reconstructed. Just as compression is performed using pixel correlation between frames in a 2D video, this paper compresses 3D PCFs by estimating the non-rigid 3D motion of a 3D object in a 3D PC. The proposed algorithm can be regarded as an extension of the 2D motion estimation of a rigid local region in a 2D plane to the 3D motion estimation of a non-rigid object (human) in 3D space. Experimental results show that the proposed method can successfully compress 3D PC sequences. If it is used together with a PC compression technique such as MPEG PCC (point cloud compression) in the future, a system with high compression efficiency may be configured.

Background While handgrip strength is associated with osteoporosis in the older population and muscle weakness is related to a reduction in bone mineral density, no study has yet assessed the association between relative hand grip strength (RHGS) and osteoporosis in the older Korean population. This study assessed the associations between RHGS and osteoporosis in Korean older women aged over 60 years. Methods We used data of 4,179 older women from the Korea National Health and Nutrition Examination Survey (KNHANES) from 2014 to 2018. We applied binomial logistic regression to identify an association between RHGS and osteoporosis while controlling for other covariates such as age; socioeconomic status; smoking behavior; alcohol consumption, laboratory test results; and the prevalence of hypertension, diabetes mellitus, thyroid disease, and obesity. Results RHGS was significantly associated with osteoporosis of the left hand in older Korean women. RHGS levels 2 and 4 of the left hand showed an inverse association with the prevalence of osteoporosis in female participants aged 60–69 years (odds ratio [OR]=0.637; 95% confidence interval [CI], 0.452–0.898; p=0.010; and OR=0.496; 95% CI, 0.258–0.956; p=0.036, respectively) but not in those aged over 70 years and in the right hand. Conclusion osteoporosis was significantly associated with left-hand RHGS in 60–69-year-old women, and the osteoporosis risks decreased by approximately 36.3% and 50.4% in women with RHGS levels 2 and 4, respectively. RHGS may be used to predict osteoporosis in pre-clinical settings such as public health care institutes.

Abstract Contamination on two-dimensional (2D) crystal surfaces poses serious limitations on fundamental studies and applications of 2D crystals. Surface residues induce uncontrolled doping and charge carrier scattering in 2D crystals, and trapped residues in mechanically assembled 2D vertical heterostructures often hinder coupling between stacked layers. Developing a process that can reduce the surface residues on 2D crystals is important. In this study, we explored the use of atomic force microscopy (AFM) to remove surface residues from 2D crystals. Using various transmission electron microscopy (TEM) investigations, we confirmed that surface residues on graphene samples can be effectively removed via contact-mode AFM scanning. The mechanical cleaning process dramatically increases the residue-free areas, where high-resolution imaging of graphene layers can be obtained. We believe that our mechanical cleaning process can be utilized to prepare high-quality 2D crystal samples with minimum surface residues.

Triple-negative breast cancer is more aggressive than other types of breast cancer. Protein kinase R (PKR), which is activated by dsRNA, is known to play a role in doxorubicin-mediated apoptosis; however, its role in DNA damage-mediated apoptosis is not well understood. In this study, we investigated the roles of PKR and its downstream players in doxorubicin-treated HCC1143 triple-negative breast cancer cells. Doxorubicin treatment induces DNA damage and apoptosis. Interestingly, doxorubicin treatment induced the phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) via PKR, whereas the inhibition of PKR with inhibitor C16 reduced eIF2α phosphorylation. Under these conditions, doxorubicin-mediated DNA fragmentation, cell death, and poly(ADP ribose) polymerase and caspase 7 levels were recovered. In addition, phosphorylation of checkpoint kinase 1 (CHK1), which is known to be involved in doxorubicin-mediated DNA damage, was increased by doxorubicin treatment, but blocked by PKR inhibition. Protein translation was downregulated by doxorubicin treatment and upregulated by blocking PKR phosphorylation. These results suggest that PKR activation induces apoptosis by increasing the phosphorylation of eIF2α and CHK1 and decreasing the global protein translation in doxorubicin-treated HCC1143 triple-negative breast cancer cells.

A sequence of 3D models generated using volumetric capture has the advantage of retaining the characteristics of dynamic objects and scenes. However, in volumetric data, since 3D mesh and texture are synthesized for every frame, the mesh of every frame has a different shape, and the brightness and color quality of the texture is various. This paper proposes an algorithm to consistently create a mesh of 4D volumetric data using dynamic reconstruction. The proposed algorithm comprises remeshing, correspondence searching, and target frame reconstruction by key frame deformation. We make non-rigid deformation possible by applying the surface deformation method of the key frame. Finally, we propose a method of compressing the target frame using the target frame reconstructed using the key frame with error rates of up to 98.88% and at least 20.39% compared to previous studies. The experimental results show the proposed method’s effectiveness by measuring the geometric error between the deformed key frame and the target frame. Further, by calculating the residual between two frames, the ratio of data transmitted is measured to show a compression performance of 18.48%.

Due to the amount of transmitted data and the security of personal or private information in wireless communication, there are cases where the information for a multimedia service should be directly transferred from the user’s device to the cloud server without the captured original images. This paper proposes a new method to generate 3D (dimensional) keypoints based on a user’s mobile device with a commercial RGB camera in a distributed computing environment such as a cloud server. The images are captured with a moving camera and 2D keypoints are extracted from them. After executing feature extraction between continuous frames, disparities are calculated between frames using the relationships between matched keypoints. The physical distance of the baseline is estimated by using the motion information of the camera, and the actual distance is calculated by using the calculated disparity and the estimated baseline. Finally, 3D keypoints are generated by adding the extracted 2D keypoints to the calculated distance. A keypoint-based scene change method is proposed as well. Due to the existing similarity between continuous frames captured from a camera, not all 3D keypoints are transferred and stored, only the new ones. Compared with the ground truth of the TUM dataset, the average error of the estimated 3D keypoints was measured as 5.98 mm, which shows that the proposed method has relatively good performance considering that it uses a commercial RGB camera on a mobile device. Furthermore, the transferred 3D keypoints were decreased to about 73.6%.

Abstract This study proposes the unique method to analyze the cleanliness of the fine metal mask (FMM) used in OLED display manufacturing after FMM cleaning process. We developed a FMM-mimic microstructure as a substitute for the FMM, which can be used for the evaluation of cleaning efficiency. The FMM-mimic microstructure was fabricated using a combination of photolithography, reactive ion etching, anodic bonding and sand blasting processes. To demonstrate the proposed cleanliness analytical method, a 1.4 μm-thick Tris-(8-hydroxyquinoline) aluminum (Alq3) film was deposited on the FMM-mimic microstructure as a contaminant by vacuum thermal evaporation. The Alq3-deposited FMM-mimic microstructure was cleaned by N-methyl-2-pyrrolidone (NMP) with changing cleaning time. We analyzed the residual contaminants on the FMM-mimic microstructure using a fluorescence microscope. The developed FMM-mimic microstructure proves very convenient for inspecting the residual contaminant inside the gap through the transparent glass by general optical and fluorescence microscopy.

In recent years, there has been considerable interest in the use of cell-free supernatant of probiotics culture for nutritional and functional applications. In this study, we investigated the effect of the cell-free supernatant from Lactobacillus gasseri BNR17 (CFS) on anti-melanogenesis and reducing oxidative stress in B16-F10 murine melanoma cells and HaCaT human keratinocytes. Treatment with CFS significantly inhibited the production of extracellular and intracellular melanin without cytotoxicity during melanogenesis induced by the α-MSH in B16-F10 cells. The CFS dramatically reduced tyrosinase activity and the melanogenesis-related gene expression. Further, it showed antioxidative effects in a dose-dependent manner in DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assays and significantly increased the mRNA levels of HO-1 and CAT in HaCaT cells. Furthermore, the CFS increased HO-1 and anti-oxidative-related gene expression during H2O2-induced oxidative stress in HaCaT cells. Together, this study suggests that the CFS reduces hyperpigmentation and inhibits oxidative stress, and thus can be used as a potential skincare product in the future.

Purpose. Previous studies reported the relation of osteoarthritis (OA) and hypertension (HTN) mostly in postmenopausal women. This study aimed to identify the association between OA and HTN in pre- and postmenopausal women. Methods. We used data of 4,627 middle-aged (40–59 years) women from the Korea National Health and Nutrition Examination Survey (KNHANES) from 2012 to 2016. Chi-square and t-test compared the characteristics of the participants. Binomial logistic regression was used to identify an association between OA and HTN under controlling covariates such as age, tobacco smoking, alcohol consumption, and obesity. Results. There were 1,859 participants with non-OA and menopause, 104 with OA and nonmenopause, and 375 with OA and menopause, respectively. The number of women with OA and HTN was 129. OA was significantly associated with HTN diagnosis in postmenopausal women under controlling covariates (odds ratio: 1.408, 95% CI: 1.092–1.815, p=0.008). However, this relationship was weakened in premenopausal women (odds ratio: 1.651, 95% CI: 0.950–2.869, p=0.075). Conclusion. In conclusion, women with HTN showed a distinct association with OA than the normotensives, and this relationship was more apparent among postmenopausal women. Further research is needed for a preventive approach.

This study estimated the economic burden of people with brain disability in Korea during 2008-2011 using nationally representative data and was conducted to use the results as an evidence for determining the resources allocation of people with brain disability. We used a prevalence-based approach to estimate the economic burden, classified by direct costs (medical costs and nonmedical costs) and indirect costs (productivity loss of morbidity and premature death). Data from the National Health Insurance Service, the National Disability Registry, the National survey on persons with disabilities, the Korea National Statistical Office’s records of causes of death, and the Labor Statistics were used to calculate direct and indirect costs. The treated prevalence of brain disability increased from 0.26% (2008) to 0.35% (2011). Total economic burden of brain-related diseases was US$1.88 billion in 2008 and increased to US$2.90 billion in 2011, with a 54% rate of increase. The economic burden of all diseases, which was 1.2 to 1.4 times higher than that of brain-related diseases, accounted for US$2.61 billion in 2008 and US$3.62 billion in 2011, increasing by 39%. Owing to the growing occurrence of brain disability, the annual prevalence and related costs are increasing. Health management programs are necessary to reduce the economic burden of brain disability in Korea.

Abstract The atomic or molecular assembly on 2D materials through the relatively weak van der Waals interaction is quite different from the conventional heteroepitaxy and may result in unique growth behaviors. Here, it is shown that straight 1D cyanide chains display universal epitaxy on hexagonal 2D materials. A universal oriented assembly of cyanide crystals (AgCN, AuCN, and Cu0.5Au0.5CN) is observed, where the chains are aligned along the three zigzag lattice directions of various 2D hexagonal crystals (graphene, h‐BN, WS2, MoS2, WSe2, MoSe2, and MoTe2). The potential energy landscape of the hexagonal lattice induces this preferred alignment of 1D chains along the zigzag lattice directions, regardless of the lattice parameter and surface elements as demonstrated by first‐principles calculations and parameterized surface potential calculations. Furthermore, the oriented microwires can serve as crystal orientation markers, and stacking‐angle‐controlled vertical 2D heterostructures are successfully fabricated by using them as markers. The oriented van der Waals epitaxy can be generalized to any hexagonal 2D crystals and will serve as a unique growth process to form crystals with orientations along the zigzag directions by epitaxy.

Purpose. We investigated the association between occupational physical activity, leisure-time physical activity, and sedentary lifestyle with hypertension by adherence with aerobic exercise in middle-aged and elderly women. Methods. A cross-sectional analysis was performed using Korea National Health and Nutrition Examination Survey (KNHANES), a nationally representative data between 2016 and 2017. A total of 4,241 women aged 40 years or older were included. Hypertension diagnosed by physician and exercise status was asked by questionnaires. Results. Mean age of the participants was 58.4 (±11.4, range: 40∼80 years). There were 1,681 (39.6%) women in the aerobic activity adherence group. In the logistic regression analysis with adjustment for confounding factors, frequency of occupational physical activity (OPA) level (OR 1.931; p=0.048, in ≤4 per week group), walking frequency (OR 0.436; p=0.001, in 5∼7 days per week walking group compared with never walking group) in the aerobic activity adherence group, sitting hours (OR 1.849; 95% CI: 1.279–2.673, p=0.001, in 13 hours or longer group compared with 6 hours or less sitting hours group), and muscle strengthening exercises (OR 0.554; 95% CI: 0.353–0.870, p=0.010, 1∼4 days per week compared with never) in the nonadherence group were significantly associated with hypertension. Conclusions. In the aerobic activity adherence group, further research is needed to identify the influence of occupational physical activity. In the aerobic activity nonadherence group, decreasing sitting hours and increasing endurance exercise may be helpful.

Having the advantage of eco-friendly decomposition, bioplastics could be used to replace petroleum-based plastics. In particular, poly(3-hydroxybutyrate) (PHB) is one of the most commercialized bioplastics, however, necessitating the introduction of PHB-degrading bacteria for its effective disposal. In this study, Microbulbifer sp. SOL66 (94.18% 16S rRNA with similarity to Microbulbifer hydrolyticus) demonstrated the highest degradation activity among five newly screened Microbulbifer genus strains. Microbulbifer sp. SOL66 showed a rapid degradation yield, reaching 98% in 4 days, as monitored by laboratory scale, gas chromatography-mass spectrometry, scanning electron microscopy, gel permeation chromatography, and Fourier transform infrared spectroscopy. The PHB film was completely degraded within 7 days at 37 °C in the presence of 3% NaCl. When 1% xylose and 0.4% ammonium sulfate were added, the degradation activity increased by 17% and 24%, respectively. In addition, this strain showed biodegradability on pellets of poly(3-hydroxybutyrate-co-4-hydroxybutyrate), as confirmed by weight loss and physical property changes. We confirmed that Microbulbifer sp. SOL66 has a great ability to degrade PHB, and has rarely been reported to date.

Protein synthesis is important for maintaining cellular homeostasis under various stress responses. In this study, we screened an anticancer drug library to select compounds with translational repression functions. AZD8055, an ATP-competitive mechanistic target of rapamycin complex 1/2 (mTORC1/2) inhibitor, was selected as a translational suppressor. AZD8055 inhibited protein synthesis in mouse embryonic fibroblasts and hepatocellular carcinoma HepG2 cells. Extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) were activated during the early phase of mTORC1/2 inhibition by AZD8055 treatment. Combined treatment of AZD8055 with the MAPK kinase1/2 (MEK1/2) inhibitor refametinib or the p38 inhibitor SB203580 markedly decreased translation in HepG2 cells. Thus, the inhibition of ERK1/2 or p38 may enhance the efficacy of AZD8055-mediated inhibition of protein synthesis. In addition, AZD8055 down-regulated the phosphorylation of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), and AZD8055-induced phosphorylation of ERK1/2 and p38 had no effect on phosphorylation status of 4E-BP1. Interestingly, AZD8055 modulated the 4E-BP1 mRNA pool by up-regulating ERK1/2 and p38 pathways. Together, these results suggest that AZD8055-induced activation of MAPKs interferes with inhibition of protein synthesis at an early stage of mTORC1/2 inhibition, and that it may contribute to the development of resistance to mTORC1/2 inhibitors.

Recently, three-dimensional printing (3DP) technology has been widely adopted in biology and biomedical applications, thanks to its capacity to readily construct complex 3D features. Using hot-melt extrusion 3DP, scaffolds for bone tissue engineering were fabricated using a composite of biodegradable polycaprolactone (PCL) and hydroxyapatite (HA). However, there are hardly any published reports on the application of the fused deposition modeling (FDM) method using feed filaments, which is the most common 3D printing method. In this study, we report on the fabrication and characterization of biocompatible filaments made of polycaprolactone (PCL)/hydroxyapatite (HA), a raw material mainly used for bone scaffolds, using FDM 3D printing. A series of filaments with varying HA content, from 5 to 25 wt.%, were fabricated. The mechanical and electrical properties of the various structures, printed using a commercially available 3D printer, were examined. Specifically, mechanical tensile tests were performed on the 3D-printed filaments and specimens. In addition, the electrical dielectric properties of the 3D-printed structures were investigated. Our method facilitates the fabrication of biocompatible structures using FDM-type 3DP, creating not only bone scaffolds but also testbeds for mimicking bone structure that may be useful in various fields of study.

Arctic bacteria employ various mechanisms to survive harsh conditions, one of which is to accumulate carbon and energy inside the cell in the form of polyhydroxyalkanoate (PHA). Whole-genome sequencing of a new Arctic soil bacterium Pseudomonas sp. B14-6 revealed two PHA-production-related gene clusters containing four PHA synthase genes (phaC). Pseudomonas sp. B14-6 produced poly(6% 3-hydroxybutyrate-co-94% 3-hydroxyalkanoate) from various carbon sources, containing short-chain-length PHA (scl-PHA) and medium-chain-length PHA (mcl-PHA) composed of various monomers analyzed by GC-MS, such as 3-hydroxybutyrate, 3-hydroxyhexanoate, 3-hydroxyoctanoate, 3-hydroxydecanoate, 3-hydroxydodecenoic acid, 3-hydroxydodecanoic acid, and 3-hydroxytetradecanoic acid. By optimizing the PHA production media, we achieved 34.6% PHA content using 5% fructose, and 23.7% PHA content using 5% fructose syrup. Differential scanning calorimetry of the scl-co-mcl PHA determined a glass transition temperature (Tg) of 15.3 °C, melting temperature of 112.8 °C, crystallization temperature of 86.8 °C, and 3.82% crystallinity. In addition, gel permeation chromatography revealed a number average molecular weight of 3.6 × 104, weight average molecular weight of 9.1 × 104, and polydispersity index value of 2.5. Overall, the novel Pseudomonas sp. B14-6 produced a polymer with high medium-chain-length content, low Tg, and low crystallinity, indicating its potential use in medical applications.

Objective The optimal treatment methods for thoracolumbar burst fracture with intact neurology are not established yet. Spinal canal integrity, sagittal balance and anterior column intactness are very important for successful outcome in this type of injury. There is no study analyzing restoration of these parameters by low pressure restoration using postural pillow reduction and lordotic posterior column compressive percutaneous transpedicular screw fixation and this study analyzes canal remodeling, spinal balance and anterior column intactness after this procedure. Methods The surgical procedure included three different elements: (1) preoperative postural pillow reduction for 1-2 days, (2) augmentation of fractured vertebra by polymethylmethacrylate (PMMA) in osteoporotic bone or by non-PMMA materials in non-osteoporotic bone, and (3) lordotic, posterior column compressive, percutaneous transpedicular screw fixation. We measured anterior vertebral height, canal size and lordotic angle preoperatively, immediate postoperatively and after 6 months in 34 patients treated with this technique and were analyzed. Results Of 34 patients 17 were male. The mean age was 52.03±12.51 years. They were followed for 30.68±11.67 months on average. At 6 months, preoperative canal stenosis of 44% remodeled to 12%, preoperative anterior vertebral height of 44% increased to 77% and preoperative average kyphosis of 14 degrees corrected to 3.4 degrees No neurological deterioration noted. Functionally all patients returned to their previous status. Conclusion The postural pillow reduction and lordotic posterior column compressive percutaneous screw fixation in patients with neurologically intact thoracolumbar burst fracture is effective and safe.

Traditional open and microscopic approaches for lumbar discectomy in cauda equina syndrome are associated with retraction of thecal sac and nerve root which was already compromised. Our study looks upon a case of cauda equina syndrome due to massive disc herniation which was operated by percutaneous endoscopic transforaminal lumbar discectomy (PETLD) using outside in technique. The procedure is done under local anesthesia with minimal soft tissue damage and allows early rehabilitation with the better aesthetic outcome. PETLD is a safe and effective alternative to emergently decompress the lumbar spine with prompt recovery.

Bar-code (tag) microarrays of yeast gene-deletion collections facilitate the systematic identification of genes required for growth in any condition of interest. Anti-sense strands of amplified bar-codes hybridize with ~10,000 (5,000 each for up- and down-tags) different kinds of sense-strand probes on an array. In this study, we optimized the hybridization processes of an array for fission yeast. Compared to the first version of the array (11 µm, 100K) consisting of three sectors with probe pairs (perfect match and mismatch), the second version (11 µm, 48K) could represent ~10,000 up-/down-tags in quadruplicate along with 1,508 negative controls in quadruplicate and a single set of 1,000 unique negative controls at random dispersed positions without mismatch pairs. For PCR, the optimal annealing temperature (maximizing yield and minimizing extra bands) was 58℃ for both tags. Intriguingly, up-tags required 3× higher amounts of blocking oligonucleotides than down-tags. A 1:1 mix ratio between up- and down-tags was satisfactory. A lower temperature (25℃) was optimal for cultivation instead of a normal temperature (30℃) because of extra temperature-sensitive mutants in a subset of the deletion library. Activation of frozen pooled cells for >1 day showed better resolution of intensity than no activation. A tag intensity analysis showed that tag(s) of 4,316 of the 4,526 strains tested were represented at least once; 3,706 strains were represented by both tags, 4,072 strains by up-tags only, and 3,950 strains by down-tags only. The results indicate that this microarray will be a powerful analytical platform for elucidating currently unknown gene functions.

Polymethyl methacrylate (PMMA)-based bone cement (BC) is a key material in joint replacement surgery that transfers external forces from the implant to the bone while allowing their robust binding. To quantitatively evaluate the effect of polymerization on the thermomechanical properties of the BC and on the interaction characteristics with the bone ceramic hydroxyapatite (HAp), molecular dynamics simulations were performed. The mechanical stiffness of the BC material under external loading increased gradually with the crosslinking reaction occurrence, indicating increasing load transfer between the constituent molecules. In addition, as the individual Methyl Methacrylate (MMA) segments were interconnected in the system, the freedom of the molecular network was largely suppressed, resulting in more thermally stable structures. Furthermore, the pull-out tests using HAp/BC bilayer models under different constraints (BC at 40% and 85%) revealed the cohesive characteristics of the BC with the bone scaffold in molecular detail. The stiffness and the fracture energy increased by 32% and 98%, respectively, with the crosslink density increasing.

Polyhydroxyalkanoates (PHAs) are attractive new bioplastics for the replacement of plastics derived from fossil fuels. With their biodegradable properties, they have also recently been applied to the medical field. As poly(3-hydroxybutyrate) produced by wild-type Ralstonia eutropha has limitations with regard to its physical properties, it is advantageous to synthesize co- or terpolymers with medium-chain-length monomers. In this study, tung oil, which has antioxidant activity due to its 80% α-eleostearic acid content, was used as a carbon source and terpolymer P(53 mol% 3-hydroxybytyrate-co-2 mol% 3-hydroxyvalerate-co-45 mol% 3-hydroxyhexanoate) with a high proportion of 3-hydroxyhexanoate was produced in R. eutropha Re2133/pCB81. To avail the benefits of α-eleostearic acid in the tung oil-based medium, we performed partial harvesting of PHA by using a mild water wash to recover PHA and residual tung oil on the PHA film. This resulted in a film coated with residual tung oil, showing antioxidant activity. Here, we report the first application of tung oil as a substrate for PHA production, introducing a high proportion of hydroxyhexanoate monomer into the terpolymer. Additionally, the residual tung oil was used as an antioxidant coating, resulting in the production of bioactive PHA, expanding the applicability to the medical field.

The overuse of antibiotics has led to the emergence of multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). MRSA is difficult to kill with a single antibiotic because it has evolved to be resistant to various antibiotics by increasing the PBP2a (mecA) expression level, building up biofilm, introducing SCCmec for multidrug resistance, and changing its membrane properties. Therefore, to overcome antibiotic resistance and decrease possible genetic mutations that can lead to the acquisition of higher antibiotic resistance, drug combination therapy was applied based on previous results indicating that MRSA shows increased susceptibility to free fatty acids and surfactants. The optimal ratio of three components and the synergistic effects of possible combinations were investigated. The combinations were directly applied to clinically isolated strains, and the combination containing 15 μg/mL of oxacillin was able to control SCCmec type III and IV isolates having an oxacillin minimum inhibitory concentration (MIC) up to 1024 μg/mL; moreover, the combination with a slightly increased oxacillin concentration was able to kill SCCmec type II. Phospholipid analysis revealed that clinical strains with higher resistance contained a high portion of 12-methyltetradecanoic acid (anteiso-C15:0) and 14-methylhexadecanoic acid (anteiso-C17:0), although individual strains showed different patterns. In summary, we showed that combinatorial therapy with a low concentration of oxacillin controlled different laboratory and highly diversified clinical MRSA strains.

Surface initiated atom transfer radical polymerization (SI-ATRP) documented a simple but efficient technique to grow a dense polymer layer on any surface. Gold nanoparticles (AuNPs) give a broad surface to immobilize sulfhyryl group-containing initiators for SI-ATRP; in addition, AuNPs are the major nanoparticulate carriers for delivery of anti-cancer therapeutics, since they are biocompatible and bioinert. In this work, AuNPs with a disulfide initiator were polymerized with sulfoethyl methacrylate by SI-ATRP to decorate the particles with anionic corona, and branched polyethyeleneimine (PEI) and siRNA were sequentially layered onto the anionic corona of AuNP by electrostatic interaction. The in vitro anti-cancer effect confirmed that AuNP with anionic corona showed higher degrees of apoptosis as well as suppression of the oncogene expression in a siRNA dose-dependent manner. The in vivo study of tumor-bearing nude mice revealed that mice treated with c-Myc siRNA-incorporated AuNPs showed dramatically decreased tumor size in comparison to those with free siRNA for 4 weeks. Furthermore, histological examination and gene expression study revealed that the decorated AuNP significantly suppressed c-Myc expression. Thus, we envision that the layer-by-layer assembly on the anionic brushes can be potentially used to incorporate nucleic acids onto metallic particles with high transfection efficiency.