Harnessing a paper-folding mechanism for reconfigurable DNA origami.

The paper-folding mechanism has been widely adopted in building of reconfigurable macroscale systems because of its unique capabilities and advantages in programming variable shapes and stiffness into a structure1-5. However, it has barely been exploited in the construction of molecular-level systems owing to the lack of a suitable design principle, even though various dynamic structures based on DNA self-assembly6-9 have been developed10-23. Here we propose a method to harness the paper-folding mechanism to create reconfigurable DNA origami structures. The main idea is to build a reference, planar wireframe structure24 whose edges follow a crease pattern in paper folding so that it can be folded into various target shapes. We realized several paper-like folding and unfolding patterns using DNA strand displacement25 with high yield. Orthogonal folding, repeatable folding and unfolding, folding-based microRNA detection and fluorescence signal control were demonstrated. Stimuli-responsive folding and unfolding triggered by pH or light-source change were also possible. Moreover, by employing hierarchical assembly26 we could expand the design space and complexity of the paper-folding mechanism in a highly programmable manner. Because of its high programmability and scalability, we expect that the proposed paper-folding-based reconfiguration method will advance the development of complex molecular systems.

Exercise-induced Hypertension and Carotid Intima-media Thickness in Male Marathon Runners.

This study aimed to identify the relationship between exercise-induced hypertension and carotid artery intima-media thickness in long-distance runners. Sixty healthy male runners aged 40 to 60 years were assigned to the following three groups based on resting blood pressure and maximal systolic blood pressure during a maximal exercise test: normal blood pressure response, exercise-induced hypertension, and complex hypertension. An exaggerated systolic blood pressure response was defined as a maximal systolic blood pressure+≥+210 mmHg during the maximal exercise test, while carotid intima-media thickness was measured using B-mode ultrasonography. The carotid intima-media thickness mean values were the highest in the complex hypertension group (0.72±0.11 mm), followed by exercise-induced hypertension (0.62±0.12 mm) and normal blood pressure groups (0.55±0.13 mm), with a significant difference between the groups (p+<+0.002). In linear regression analysis, the mean intima-media thickness was independently associated with age (p=0.015) and maximal systolic blood pressure (p=0.046) but not with resting systolic blood pressure. These results suggest that exercise-induced hypertension is associated with carotid intima-media thickness, a surrogate marker of cardiovascular disease, in long-distance runners. Therefore, evaluating the blood pressure response during exercise is important for the early detection of potential cardiovascular disease risks in long-distance runners.

Excessive blood pressure rise and cardiovascular remodeling in marathon runners.

Exercise-induced hypertension (EIH) is thought to be associated with increased cardiovascular (CV) risks. However, no previous studies have investigated the effects of EIH on CV systems in marathon runners without CV risk factors using both 24-hr ambulatory blood pressure (BP) monitoring and exercise stress echocardiography (ESE). This study firstly described differences in CV adaptations according to EIH assessed by both exams. Marathon runners between 35 and 64 years of age without CV risk factors were eligible. All the participants underwent both 24-hr ambulatory BP monitoring and ESE. EIH was defined as a maximal exercise systolic BP ≥210 mmHg. The EIH group (n = 19) had shorter training history and higher exercise intensity compared to the non-EIH group (n = 23). The average systolic BP was higher in the EIH group than in the non-EIH group. Left cardiac chamber size and left ventricular mass (LVM) were also higher in the EIH group compared to the non-EIH group. Maximal BP during ESE was positively correlated with both parameters. Exaggerated BP response during exercise needs to be monitored for pre-emptive measurements before it results in progressive cardiovascular maladaptation.

Photolithographic patterning on multi-wavelength quantum dot film of the improved conversion efficiency for digital holography.

A triple-wavelength patterned quantum dot film was fabricated for the light source of digital holography to improve both the axial measurement range and noise reduction. The patterned quantum dot film was fabricated after optimizing the photolithography process condition based on the UV-curable quantum dot solution, which was capable of multiple patterning processes. In addition, an optimized pattern structure was developed by adding TiO2 nanoparticles to both the quantum dot and bank layers to increase the scattering effect for the improved photoluminescence intensity. Finally, the newly developed light source with the balanced spectral distribution was applied to the digital holography, rendering it applicable as an improved light source.

Geometric analysis algorithm based on a neural network with localized simulation data for nano-grating structure using Mueller matrix spectroscopic ellipsometry.

Mueller matrix spectroscopic ellipsometry (MMSE) is a nondestructive tool for nanostructure analysis, and recently the enhanced computational power, combining neural networks and simulation data, enhance its analysis ability on more complex geometries. This study introduces a deep learning method to realize fast and accurate analysis; predicting nanostructure parameters by pairing Mueller matrices with relatively limited library data and then applying neural network algorithm. Thus, it was realized to predict the width and height of 1D grating structure with an accuracy of MAE below 0.1 nm through the proposed two-step prediction algorithm. Finally, experimental validation on SiO2 grating of 38 nm width and 100 nm height showed a good agreement in the dimensions with reasonable range compared to those measured by scanning electron microscopy.

Modulating the chemo-mechanical response of structured DNA assemblies through binding molecules.

Recent advances in DNA nanotechnology led the fabrication and utilization of various DNA assemblies, but the development of a method to control their global shapes and mechanical flexibilities with high efficiency and repeatability is one of the remaining challenges for the realization of the molecular machines with on-demand functionalities. DNA-binding molecules with intercalation and groove binding modes are known to induce the perturbation on the geometrical and mechanical characteristics of DNA at the strand level, which might be effective in structured DNA assemblies as well. Here, we demonstrate that the chemo-mechanical response of DNA strands with binding ligands can change the global shape and stiffness of DNA origami nanostructures, thereby enabling the systematic modulation of them by selecting a proper ligand and its concentration. Multiple DNA-binding drugs and fluorophores were applied to straight and curved DNA origami bundles, which demonstrated a fast, recoverable, and controllable alteration of the bending persistence length and the radius of curvature of DNA nanostructures. This chemo-mechanical modulation of DNA nanostructures would provide a powerful tool for reconfigurable and dynamic actuation of DNA machineries.

The Impact of Light Wavelength and Darkness on Metabolite Profiling of Korean Ginseng: Evaluating Its Anti-Cancer Potential against MCF-7 and BV-2 Cell Lines.

Korean ginseng is a source of functional foods and medicines; however, its productivity is hindered by abiotic stress factors, such as light. This study investigated the impacts of darkness and different light wavelengths on the metabolomics and anti-cancer activity of ginseng extracts. Hydroponically-grown Korean ginseng was shifted to a light-emitting diodes (LEDs) chamber for blue-LED and darkness treatments, while white fluorescent (FL) light treatment was the control. MCF-7 breast cancer and lipopolysaccharide (LPS)-induced BV-2 microglial cells were used to determine chemo-preventive and neuroprotective potential. Overall, 53 significant primary metabolites were detected in the treated samples. The levels of ginsenosides Rb1, Rb2, Rc, Rd, and Re, as well as organic and amino acids, were significantly higher in the dark treatment, followed by blue-LED treatment and the FL control. The dark-treated ginseng extract significantly induced apoptotic signaling in MCF-7 cells and dose-dependently inhibited the NF-κB and MAP kinase pathways in LPS-induced BV-2 cells. Short-term dark treatment increased the content of Rd, Rc, Rb1, Rb2, and Re ginsenosides in ginseng extracts, which promoted apoptosis of MCF-7 cells and inhibition of the MAP kinase pathway in BV-2 microglial cells. These results indicate that the dark treatment might be effective in improving the pharmacological potential of ginseng.

FBI-1 inhibits epithelial-to-mesenchymal transition, migration, and invasion in lung adenocarcinoma A549 cells by downregulating transforming growth factor-ß1 signaling pathway.

The factor binding inducer of short transcripts-1 (FBI-1) is a POZ-domain Kruppel-like (POK) family of transcription factors and is known as a proto-oncogene or tumor suppressor in various carcinomas. However, the role of FBI-1 on epithelial-to-mesenchymal transition (EMT) and invasiveness in lung cancer remains unknown. Preliminarily, clinical data such as tissue microarray, Kaplan-Meier, and Oncomine were analyzed to confirm the correlation between lung cancer metastasis and FBI-1. To investigate the function of FBI-1 in EMT in lung cancer, EMT was measured in FBI-1-deficient or FBI-1-overexpressing cells. FBI-1 showed decreased expression in tumors metastasized to lymph nodes than in the primary tumor. In addition, it was also associated with improved survival rates of lung cancer patients. FBI-1 knockdown improved E-to-N-cadherin switching, migration, and invasion in A549 cells, similar to the initiation of EMT stimulated by transforming growth factor- ß1 (TGF-ß1). In contrast, overexpression of FBI-1 inhibited the transcription and activation of Smad2, thereby interfering with EMT, despite stimulation by TGF-ß1. These results suggest that FBI-1 plays a negative role in EMT in lung cancer via the TGF-ß1 signaling pathway, implying its use as a new potential therapeutic target and diagnostic indicator for early stage of lung cancer metastasis.

Accelerating AFM Characterization via Deep-Learning-Based Image Super-Resolution.

Atomic force microscopy (AFM) is one of the most popular imaging and characterizing methods applicable to a wide range of nanoscale material systems. However, high-resolution imaging using AFM generally suffers from a low scanning yield due to its method of raster scanning. Here, a systematic method of data acquisition and preparation combined with a deep-learning-based image super-resolution, enabling rapid AFM characterization with accuracy, is proposed. Its application to measuring the geometrical and mechanical properties of structured DNA assemblies reveals that around a tenfold reduction in AFM imaging time can be achieved without significant loss of accuracy. Through a transfer learning strategy, it can be efficiently customized for a specific target sample on demand.

Age and sex-specific associations between depressive symptoms, body mass index and cognitive functioning among Korean middle-aged and older adults: a cross-sectional analysis.

BACKGROUND: Although depression and body weight have been noted as important predictors of cognitive health, it remains unclear how age and sex influence the mechanism by which depressive symptoms and body weight are associated with cognitive functioning. This study examined whether and how the relationships between depressive symptoms and cognitive functioning mediated by body mass index (BMI) differ in terms of age and sex. METHODS: A cross-sectional analysis of a large sample of population-based data (N = 5,619; mean age 70.73 [± 9.07]), derived from the Korean Longitudinal Study of Aging, was conducted with hierarchical mediated-moderation regressions and a PROCESS macro approach in SPSS. Depressive symptoms were measured through the 10-item Center for Epidemiologic Studies Depression (CES-D) scale, and cognitive functioning was assessed with the Korean Mini-Mental State Examination (K-MMSE). RESULTS: The results showed that depressive symptoms were significantly associated with cognitive decline directly and indirectly through reduced BMI. The estimated coefficients indicated that a one standard deviation increase in CES-D scale was associated with about 0.9 decrease in K-MMSE score. However, the indirect relationship between depressive symptoms and cognitive function through BMI emerged only in men or individuals older than 70 years. CONCLUSIONS: The findings suggest that a careful assessment of BMI is warranted for early detection and prevention of cognitive decline related to depressive symptoms, particularly among older men.

Biased Pressure: Cyclic Reinforcement Learning Model for Intelligent Traffic Signal Control.

Existing inefficient traffic signal plans are causing traffic congestions in many urban areas. In recent years, many deep reinforcement learning (RL) methods have been proposed to control traffic signals in real-time by interacting with the environment. However, most of existing state-of-the-art RL methods use complex state definition and reward functions and/or neglect the real-world constraints such as cyclic phase order and minimum/maximum duration for each traffic phase. These issues make existing methods infeasible to implement for real-world applications. In this paper, we propose an RL-based multi-intersection traffic light control model with a simple yet effective combination of state, reward, and action definitions. The proposed model uses a novel pressure method called Biased Pressure (BP). We use a state-of-the-art advantage actor-critic learning mechanism in our model. Due to the decentralized nature of our state, reward, and action definitions, we achieve a scalable model. The performance of the proposed method is compared with related methods using both synthetic and real-world datasets. Experimental results show that our method outperforms the existing cyclic phase control methods with a significant margin in terms of throughput and average travel time. Moreover, we conduct ablation studies to justify the superiority of the BP method over the existing pressure methods.

Semi-Supervised Domain Adaptation for Multi-Label Classification on Nonintrusive Load Monitoring.

Nonintrusive load monitoring (NILM) is a technology that analyzes the load consumption and usage of an appliance from the total load. NILM is becoming increasingly important because residential and commercial power consumption account for about 60% of global energy consumption. Deep neural network-based NILM studies have increased rapidly as hardware computation costs have decreased. A significant amount of labeled data is required to train deep neural networks. However, installing smart meters on each appliance of all households for data collection requires the cost of geometric series. Therefore, it is urgent to detect whether the appliance is used from the total load without installing a separate smart meter. In other words, domain adaptation research, which can interpret the huge complexity of data and generalize information from various environments, has become a major challenge for NILM. In this research, we optimize domain adaptation by employing techniques such as robust knowledge distillation based on teacher-student structure, reduced complexity of feature distribution based on gkMMD, TCN-based feature extraction, and pseudo-labeling-based domain stabilization. In the experiments, we down-sample the UK-DALE and REDD datasets as in the real environment, and then verify the proposed model in various cases and discuss the results.

Embryonic stem cell-derived photoreceptor precursor cells differentiated by coculture with RPE cells.

Purpose: To describe the derivation of photoreceptor precursor cells from human embryonic stem cells by coculture with RPE cells. Methods: Human embryonic stem cells were induced to differentiate into neural precursor cells and then cocultured with RPE cells to obtain cells showing retinal photoreceptor features. Immunofluorescent staining, reverse transcription-PCR (RT-PCR), and microarray analysis were performed to identify photoreceptor markers, and a cGMP assay was used for in vitro functional analysis. After subretinal injection in rat animal models, retinal function was determined with electroretinography and optokinetic response detection, and immunofluorescent staining was performed to assess the survival of the injected cells. Results: Cocultured cells were positive for rhodopsin, red and blue opsin, recoverin, and phosphodiesterase 6 beta on immunofluorescent staining and RT-PCR. Serial detection of stem cell-, neural precursor-, and photoreceptor-specific markers was noted in each stage of differentiation with microarray analysis. Increased cGMP hydrolysis in light-exposed conditions compared to that in dark conditions was observed. After the subretinal injection in the rats, preservation of optokinetic responses was noted up to 20 weeks, while electroretinographic response decreased. Survival of the injected cells was confirmed with positive immunofluorescence staining of human markers at 8 weeks. Conclusions: Cells showed photoreceptor-specific features when stem cell-derived neurogenic precursors were cocultured with RPE cells.

Enhancement of image sharpness and height measurement using a low-speckle light source based on a patterned quantum dot film in dual-wavelength digital holography.

A dual-wavelength single light source based on a patterned quantum dot (QD) film was developed with a 405nm LED and bandpass filters to increase color conversion efficiency as well as to decouple the two peaks of dual-wavelength emitted from the QD film. A QD film was patterned laterally with two different sizes of QDs and was combined with bandpass filters to produce a high efficiency and low-speckle dual-wavelength light source. The experimental results showed that the developed dual-wavelength light source can decrease speckle noise to improve the reconstructed image sharpness and the accuracy on height measurement in dual-wavelength digital holography.

Roots of Lithospermum erythrorhizon promotes retinal cell survival in optic nerve crush-induced retinal degeneration.

Lithospermum erythrorhizon (L. erythrorhizon), used in traditional medicine, is a potent wound healing, anti-inflammatory and antioxidant plant. However, the effects of L. erythrorhizon on retinal degenerative diseases remain unknown. Here, we explored the protective effects of L. erythrorhizon in in vitro and in vivo retinal degeneration. We found that ethanol extract of L. erythrorhizon (EELE) and the dichloromethane fraction of L. erythrorhizon (MCLE) significantly increased cell viability under glutamate/BSO-induced excitotoxicity/oxidative stress in R28 cells. Treatment with EELE and MCLE reduced the intracellular reactive oxygen species (ROS) and the levels of apoptotic proteins, such as cleaved PARP and cleaved caspase-3. Furthermore, oral administration of EELE and MCLE in an in vivo optic nerve crush mouse model decreased RGC cell death and increased retinal thickness. The major compound between EELE and MCLE was found to be lithospermic acid A (LAA), which has been shown to prevent the elevation of ROS in R28. Therefore, EELE and MCLE have protective effects against the death of retinal cells in vitro and in vivo, and the major compound, LAA, has an antioxidant effect on retinal cells, suggesting that EELE and MCLE could be beneficial agents for retinal degenerative diseases, including glaucoma.

Patients' and parents' satisfaction with, and preference for, haemophilia A treatments: a cross-sectional, multicentre, observational study.

INTRODUCTION: Reports on patients' satisfaction and preferred characteristics for treatments would be worthwhile when choosing an optimal treatment reflecting patients' perspectives. AIM: To identify the characteristics and treatment patterns of patients with haemophilia A, or their caregivers, in Korea and explore patient preferences and satisfaction with their treatment. METHODS: This cross-sectional, multicentre, observational study was conducted from April 2018 to September 2019 at six nationwide hospitals and three Korea Hemophilia Foundation clinics. Patients aged ≥16 years, or legal caregivers of paediatric patients, who had used factor VIII (FVIII) concentrates for ≥1 month were enrolled. Satisfaction with treatment was measured using the Treatment Satisfaction Questionnaire for Medication (TSQM); preference was evaluated using discrete choice experiment (DCE), with 10 series of two hypothetical treatment options created from D-efficient block design, which varied across five attributes. RESULTS: Overall, 505 patients (mean age 31 years) were enrolled in the study. Patients had received FVIII concentrate for an average of 102.9 months (prophylaxis: 53.5%; on-demand: 22.2%). Mean TSQM scores were 64.6 (effectiveness domain), 97.9 (side effects), 57.1 (convenience) and 66.8 (global satisfaction). The number of vials per injection, and the frequency of drug administration, was significantly associated with treatment satisfaction. According to DCE, simpler treatment options were preferred by patients/caregivers. CONCLUSION: The lowest satisfaction levels were shown in the treatment convenience domain. Patients/parents preferred simpler and easier treatment characteristics. In an attempt to enhance the overall satisfaction of patients and caregivers with treatment, consideration of more convenient characteristics is required in future decisions regarding treatment selection.

Investigating the sequence-dependent mechanical properties of DNA nicks for applications in twisted DNA nanostructure design.

DNA nick can be used as a design motif in programming the shape and reconfigurable deformation of synthetic DNA nanostructures, but its mechanical properties have rarely been systematically characterized at the level of base sequences. Here, we investigated sequence-dependent mechanical properties of DNA nicks through molecular dynamics simulation for a comprehensive set of distinct DNA oligomers constructed using all possible base-pair steps with and without a nick. We found that torsional rigidity was reduced by 28-82% at the nick depending on its sequence and location although bending and stretching rigidities remained similar to those of regular base-pair steps. No significant effect of a nick on mechanically coupled deformation such as the twist-stretch coupling was observed. These results suggest that the primary structural role of nick is the relaxation of torsional constraint by backbones known to be responsible for relatively high torsional rigidity of DNA. Moreover, we experimentally demonstrated the usefulness of quantified nick properties in self-assembling DNA nanostructure design by constructing twisted DNA origami structures to show that sequence design of nicks successfully controls the twist angle of structures. Our study illustrates the importance as well as the opportunities of considering sequence-dependent properties in structural DNA nanotechnology.

Comparison of Activity and Participation, and Mental and Physical Functions of Immediate Post-Acute and Distant Post-Acute Adults with Chronic Cardiac Conditions.

This study compared activity participation, and mental and physical functions of two different groups of adults with chronic cardiac conditions. Eleven participants were assessed at the immediate post-acute stage and 26 participants were at the distant post-acute stage. Participants at distant post-acute were significantly more physically active (p < .001), more activity-limited in cognition-related activities (p = .035) and reported more depressive symptoms than immediate post-acute (p = .046). No significant difference in participation level was found. More attention to functional cognition and depressive symptoms at immediate post-acute and individualized approaches to remove participation barriers in complex activities at distant post-acute are likely needed for adults with chronic cardiac conditions.

Incidence, predictors, and outcomes of distal vessel expansion on follow-up intravascular ultrasound after recanalization of chronic total occlusions using new-generation drug-eluting stents: Data from the CTO-IVUS randomized trial.

OBJECTIVES: To evaluate the incidence, predictors, and outcomes of distal vessel expansion on intravascular ultrasound (IVUS) after recanalization of chronic total occlusion (CTO) particularly using new-generation drug-eluting stent (DES). BACKGROUND: The luminal changes of narrowed vessels distal to CTO segments after recanalization using new-generation DES have rarely been studied. METHODS: This substudy of the CTO-IVUS (Chronic Total Occlusion InterVention with drUg-eluting Stents) trial included a total of 69 new-generation DES-treated CTOs with serial matched IVUS analyses at index percutaneous coronary intervention (PCI) and at 1-year follow-up. The predictors of distal vessel expansion, any increase of lumen area at the distal reference (LAdistal ) on 1-year follow-up IVUS, were evaluated by multivariable binary logistic analyses. RESULTS: Distal vessel expansion was identified in 46 (67%). Independent determinants of distal vessel expansion were proximal CTO, a smaller LAdistal at the index PCI, a greater minimal stent area-to-LAdistal (MSA-to-LAdistal ) ratio, and a greater lumen area at the distal stent edge-to-LAdistal (LAedge -to-LAdistal ) ratio. The cut-off values of a MSA-to-LAdistal ratio and a LAedge -to-LAdistal ratio predicting the distal vessel expansion by receiver operating characteristic curve analysis were 1.0 and 1.1, respectively. During the median 5.1 years, rates of target vessel revascularization, cardiac death, and stent thrombosis were similar in the distal vessel-expanded and nonexpanded groups. CONCLUSION: After opening CTO with new-generation DES, two-thirds of patients exhibited distal vessel expansion on 1-year follow-up IVUS. Expansion determinants were a proximal CTO, lower LAdistal , and larger stent areas relative to the LAdistal (modifiable procedural predictors).

Evaluation of treatment with a combination of mycophenolate mofetil and prednisolone in dogs with meningoencephalomyelitis of unknown etiology: a retrospective study of 86 cases (2009-2017).

BACKGROUND: Combination therapy with glucocorticoids and adjunctive immunomodulating drugs has been generally accepted as a standard treatment regimen for meningoencephalomyelitis of unknown etiology (MUE). We hypothesized that treatment with MMF as an adjunctive agent along with glucocorticoids would be effective and well-tolerated protocol in dogs with MUE. Eighty-six dogs with MUE between May 2009 and June 2017 were included (59 females and 27 males; mean age of 5.93 years; mean body weight of 3.83 kg). The medical records of dogs with MUE treated with prednisolone and MMF were retrospectively evaluated to determine the therapeutic response, survival time, and treatment-related adverse effects. RESULTS: A partial or complete response (CR) was recorded for 75 dogs. The overall median survival time from the initiation of treatment was 558 days. Dogs that showed CR with no relapse over the treatment period (from diagnosis to death) had significantly longer median survival times. A significantly higher mortality hazard ratio of 4.546 was recorded in dogs that failed to achieve CR. The interval between the onset of clinical signs and the clinical presentation was not significantly associated with CR, relapse rate, and survival time. Adverse effects included gastrointestinal upsets in 26 dogs (30.23%), sporadic infections in 17 dogs (19.77%), and pancreatitis in seven dogs (8.14%). CONCLUSIONS: The results suggest that adjunctive MMF treatment for MUE is safe and comparable to other immunosuppressive protocols. The treatment should focus on the achievement of CR and preventing relapse for successful management.