Fabrication of Yolk-Shell Structure with Multifarious Nanoparticles via Double-Layered Encapsulation Strategy.

The post-encapsulation method (such as single-layered encapsulation) is a promising strategy to synthesize yolk-shell structures that protect functional nanoparticles by the molecular sieving effect. However, this method exhibited limited loading capacity and nonuniform encapsulation during the co-encapsulation of various nanoparticles owing to the insufficient surface area for nanoparticle attachment. To address these limitations, we proposed a double-layered encapsulation method comprising an increased number of silica template layers and separate attachment of multifarious nanoparticles to different layers. Compared with conventional methods, this strategy can precisely adjust the ratio of encapsulated nanoparticles and increase the loading amount, which improves the functionality of yolk-shell structures, such as the photothermal properties of gold nanoparticle-encapsulated yolk-shell structures (∼69%). We describe, for the first time, the precise control of the ratio of encapsulated nanoparticles and the loading of numerous nanoparticles. Consequently, this strategy has significant potential for various applications of yolk-shell structures.

An LGR4 agonist activates the GSK­3ß pathway to inhibit RANK­RANKL signaling during osteoclastogenesis in bone marrow­derived macrophages.

The binding between receptor­activated nuclear factor­κB (RANK) and the RANK ligand (RANKL) during osteoclast development is an important target for drugs that treat osteoporosis. The leucine­rich repeat­containing G­protein­coupled receptor 4 (LGR4) acts as a negative regulator of RANK­RANKL that suppresses canonical RANK signaling during osteoclast differentiation. Therefore, LGR4 agonists may be useful in inhibiting osteoclastogenesis and effectively treating osteoporosis. In the present study, bone marrow­derived macrophages and a mouse model of RANKL­induced bone loss were used to investigate the effect of mutant RANKL (MT RANKL), which was previously developed based on the crystal structure of the RANKL complex. In the present study, the binding affinity of wild­type (WT) RANKL and MT RANKL to RANK and LGR4 was determined using microscale thermophoresis analysis, and the effect of the ligands on the AKT­glycogen synthase kinase­3ß (GSK­3ß)­nuclear factor of activated T cells, cytoplasmic, calcineurin­dependent 1 (NFATc1) signaling cascade was investigated using western blotting and confocal microscopy. In addition, the expression of LGR4 and the colocalization of LGR4 with MT RANKL were analyzed in a mouse model of RANKL­induced bone loss. The results showed that in osteoclast precursor cells, MT RANKL bound with high affinity to LGR4 and increased GSK­3ß phosphorylation independently of AKT, resulting in the inhibition of NFATc1 nuclear translocation. In the mouse model, MT RANKL colocalized with LGR4 and inhibited bone resorption. These results indicated that MT RANKL may inhibit RANKL­induced osteoclastogenesis through an LGR4­dependent pathway and this could be exploited to develop new therapies for osteoporosis.

Nanoscale Hafnium Metal-Organic Frameworks Enhance Radiotherapeutic Effects by Upregulation of Type I Interferon and TLR7 Expression.

Recent preclinical and clinical studies have highlighted the improved outcomes of combination radiotherapy and immunotherapy. Concurrently, the development of high-Z metallic nanoparticles as radiation dose enhancers has been explored to widen the therapeutic window of radiotherapy and potentially enhance immune activation. In this study, folate-modified hafnium-based metal-organic frameworks (HfMOF-PEG-FA) are evaluated in combination with imiquimod, a TLR7 agonist, as a well-defined interferon regulatory factor (IRF) stimulator for local antitumor immunotherapy. The enhancement of radiation dose deposition by HfMOF-PEG-FA and subsequent generation of reactive oxygen species (ROS) deregulates cell proliferation and increases apoptosis. HfMOF-PEG-FA loaded with imiquimod (HfMOF-PEG-FA@IMQ) increases DNA double-strand breaks and cell death, including apoptosis, necrosis, and calreticulin exposure, in response to X-ray irradiation. Treatment with this multipronged therapy promotes IRF stimulation for subsequent interferon production within tumor cells themselves. The novel observation is reported that HfMOF itself increases TLR7 expression, unexpectedly pairing immune agonist and receptor upregulation in a tumor intrinsic manner, and supporting the synergistic effect observed with the γH2AX assay. T-cell analysis of CT26 tumors following intratumoral administration of HfMOF-PEG-FA@IMQ with radiotherapy reveals a promising antitumor response, characterized by an increase in CD8+ and proliferative T cells.

Mathematical Modeling of COVID-19 Transmission and Intervention in South Korea: A Review of Literature.

South Korea implemented interventions to curb the spread of the novel coronavirus disease 2019 (COVID-19) pandemic with discovery of the first case in early 2020. Mathematical modeling designed to reflect the dynamics of disease transmission has been shown to be an important tool for responding to COVID-19. This study aimed to review publications on the structure, method, and role of mathematical models focusing on COVID-19 transmission dynamics in Korea. In total, 42 papers published between August 7, 2020 and August 21, 2022 were studied and reviewed. This study highlights the construction and utilization of mathematical models to help craft strategies for predicting the course of an epidemic and evaluating the effectiveness of control strategies. Despite the limitations caused by a lack of available epidemiological and surveillance data, modeling studies could contribute to providing scientific evidence for policymaking by simulating various scenarios.

Study on the Ventilation Method to Maintain the PM10 Concentration in a Subway Cabin below 35 µg/m3.

The city of Seoul will limit the maximum particulate matter (PM10) concentration to ≤35 µg/m3 (from 2024). Herein, a numerical parametric study was conducted on the PM removal efficiency of the heating, ventilation, and air conditioning (HVAC) filters installed in the ceiling of subway cabins. The PM10 concentration distribution was explored according to the flow rate and flow rate ratio of the air introduced into the cabin. Under the current ventilation conditions of the subway train HVAC system, the PM10 concentration was highest in the cabin central area where exhaust outlets are located and decreased toward both ends of the cabin. The indoor airflow was improved and the PM10 concentration was reduced by increasing the flow rate of the supplied air at both ends of the cabin while decreasing it in the central area. It was found that the strengthened PM10 concentration criterion of Seoul can be met by increasing the ventilation flow rate to 700 CMH (currently, 500 CMH) and the filter efficiency to 85% (currently, 70%) while maintaining the current flow rate ratio. These results are expected to be used as important reference data for reducing the PM concentration in subway cabins and thereby improving indoor air quality.

Development of a G2/M arrest high-throughput screening method identifies potent radiosensitizers.

Radiation is a powerful tool used to control tumor growth and induce an immune response; however, it is limited by damage to surrounding tissue and adverse effects such skin irritation. Breast cancer patients in particular may endure radiation dermatitis, and potentially lymphedema, after a course of radiotherapy. Radio-sensitizing small molecule drugs may enable lower effective doses of both radiation and chemotherapy to minimize toxicity to healthy tissue. In this study, we identified a novel high-throughput method for screening radiosensitizers by image analysis of nuclear size and cell cycle. In vitro assays were performed on cancer cells lines to assess combined therapeutic and radiation effects. In vivo, radiation in combination with proflavine hemisulfate led to enhanced efficacy demonstrated by improved tumor volume control in mice bearing syngeneic breast tumors. This study provides a proof of concept for utilizing G2/M stall as a predictor of radiosensitization and is the first report of a flavin acting as an X-ray radiation enhancer in a breast cancer mouse model.

Prediction of ground motion and dynamic stress change in Baekdusan (Changbaishan) volcano caused by a North Korean nuclear explosion.

Strong ground motions induce large dynamic stress changes that may disturb the magma chamber of a volcano, thus accelerating the volcanic activity. An underground nuclear explosion test near an active volcano constitutes a direct treat to the volcano. This study examined the dynamic stress changes of the magma chamber of Baekdusan (Changbaishan) that can be induced by hypothetical North Korean nuclear explosions. Seismic waveforms for hypothetical underground nuclear explosions at North Korean test site were calculated by using an empirical Green's function approach based on a source-spectral model of a nuclear explosion; such a technique is efficient for regions containing poorly constrained velocity structures. The peak ground motions around the volcano were estimated from empirical strong-motion attenuation curves. A hypothetical M7.0 North Korean underground nuclear explosion may produce peak ground accelerations of 0.1684 m/s(2) in the horizontal direction and 0.0917 m/s(2) in the vertical direction around the volcano, inducing peak dynamic stress change of 67 kPa on the volcano surface and ~120 kPa in the spherical magma chamber. North Korean underground nuclear explosions with magnitudes of 5.0-7.6 may induce overpressure in the magma chamber of several tens to hundreds of kilopascals.

Optical approach to the periodontal ligament under orthodontic tooth movement: a preliminary study with optical coherence tomography.

INTRODUCTION: Optical coherence tomography (OCT) is a diagnostic tool that can make near-histologic tomographic images without a biohazard. Due to its high resolution (average, 4 microm) and safety (using light as the source), it has been applied widely in medical fields to replace invasive biopsies. But the trials in dentistry have been restricted to mainly detecting dental caries and oral cancer. In this preliminary study for successive human studies, we tried to evaluate whether OCT can be helpful in determining tooth movement under light orthodontic forces. METHODS: Orthodontic distraction forces (0, 5, and 10 g) were applied to the mandibular incisors of 6 white rats (10 weeks old) for 5 days by using individualized loop springs (round Elgiloy, 0.018-in diameter, Rocky Mountain Orthodontics, Denver, Colo). The changed periodontal ligaments were imaged with OCT and digital intraoral radiography 2 dimensionally. Both tensile and compressive ligaments were measured and compared. RESULTS: With OCT images, we could measure changed ligaments from all directions; radiography could not show the portions overlapped by teeth. The averages of measured ligament width in OCT were larger than those from radiography in all groups. CONCLUSIONS: This preliminary study shows the possible evaluation and prediction of precise tooth responses under orthodontic forces by using real-time OCT.

All-fiber variable optical delay line for applications in optical coherence tomography: feasibility study for a novel delay line.

We have implemented an all-fiber optical delay line using two linearly chirped fiber Bragg gratings cascaded in reverse order and all-fiber optics components. The features of the proposed all-fiber based technique for variable delay line are discussed theoretically and demonstrated experimentally. The non-invasive cross-sectional images of biomedical samples as well as a transparent glass plate obtained with implemented all-fiber delay line having the axial resolution of 100 mum and the dynamic range of 50dB are presented to validates the imaging performance and demonstrate the feasibility of the delay line for optical coherence tomography.