Dong-Hyun Kim’s research while affiliated with POSTECH POHANG UNIVERSITY OF SCIENCE AND TECHNOLOGY and other places

Suppressing failure modes and optimizing protocols enable enhanced cyclability and fast chargeability in Co-free, high-Ni layered oxide cathodes.

Background Multiple factors, such as muscle fatty infiltration (FI), tendon collagen content, and collagen arrangement, determine bone-tendon interface (BTI) healing after rotator cuff (RC) repair. Purpose To evaluate the effects of systemic administration of ezetimibe-atorvastatin (EZE/ATZ) combination on muscle FI and tendon collagen density and arrangement in an RC repair rat model. Study design Controlled laboratory study. Methods A total of 26 male Sprague-Dawley rats were randomly divided equally into control and EZE/ATZ groups and subjected to RC tendon repair surgery. Postoperatively, the EZE/ATZ group rats received a combination of EZE (10 mg/kg/d) and ATZ (20 mg/kg/d) for 4 weeks, after which they were sacrificed. Oil Red O staining was used to assess FI in the supraspinatus muscle. The expression of biomarkers related to muscle atrophy and FI was measured using quantitative real-time polymerase chain reaction. For the qualitative and quantitative analysis of FI-related biomarkers, immunohistochemical staining was performed. Biomechanical and histological analyses were performed to evaluate the quality of BTI healing after RC repair. Results The EZE/ATZ group showed significantly lower FI compared with the control group ( P < .001) and significantly downregulated expression of gene markers related to muscle atrophy and FI. On histological analysis, the EZE/ATZ group exhibited increased collagen type I contents, consistent collagen arrangement ( P = .005), and significantly higher collagen density ( P = .003) compared with the control group. Biomechanical analysis of the BTI healing revealed that the EZE/ATZ group had significantly increased ultimate strength ( P = .006) compared with the control group. Conclusion Systemic EZE/ATZ administration suppressed supraspinatus FI by downregulating muscle atrophy–related and FI-related genes after RC repair. Additionally, EZE/ATZ use improved collagen biosynthesis, density, and arrangement at the BTI and significantly increased tensile strength. Clinical Relevance The results of the current study strongly advocate the use of EZE/ATZ to improve shoulder function and tendon healing after RC repair.

Glypican‐3 (GPC3) is a key diagnostic marker and therapeutic target in hepatocellular carcinoma (HCC), interacting with Wnt and Hippo/YAP pathways related to cancer proliferation. Modulating GPC3 gene expression can induce liver cancer cell death by disrupting growth factor signaling, cell adhesion, and metabolic regulation. This study presents the development of a non‐viral ultralarge porous CRISPR‐Cas9 silica nano‐depot to perform targeted GPC3 genome editing for the treatment of HCC. The synthesized ultralarge porous silica nano‐depot (UPSND) encapsulates substantial CRISPR‐Cas9‐ribonucleoprotein complexes with a remarkable 98.3% loading efficiency. The UPSND‐mediated GPC3 CRISPR‐Cas9 therapy significantly suppresses cancer cell proliferation by modulating the Wnt and Hippo/YAP pathways. The efficiency of GPC3 gene deletion is observed to be 5.1‐fold higher than that of commercial lipid‐based GPC3 CRISPR‐Cas9 in both human and murine genes, with minimal off‐target effects. In vivo systemic administration of GPC3 Cas9‐RNP@UPSND resulted in preferential accumulation within hepatic tissues in orthotopic HCC mouse models, leading to complete tumor eradication and enhancing T‐cell tumor‐infiltration. Furthermore, the GPC3 CRISPR‐Cas9@UPSND treatment exhibits superior anti‐proliferative efficacy in tumor‐growth prevention compared to Codrituzumab, as evidenced by the analysis of Ki67 and GPC3 expression, along with serum GPC3 levels. These findings underscore the translational potential of the non‐viral UPSND nanoplatform‐based CRISPR GPC3 genome editing, offering a promising targeted therapeutic strategy for HCC treatment.

Despite multimodal treatment, 90% of patients diagnosed with isocitrate dehydrogenase (IDH) wild-type glioblastoma experience tumour recurrence within 5 years. Poor prognosis is in considerable part attributed to the ability of cancer cells to infiltrate a healthy brain. We hypothesise that metabolic changes underpinning cellular crosstalk between astrocytes and glioblastoma cells isolated from the invasive margin within a physiologically representative in-vitro tumour microenvironment may reveal therapeutic targets to prevent or delay glioblastoma recurrence. This study used advanced analytical techniques to establish baseline metabolomic profiles for eGFP-tagged primary glioblastoma cells isolated from the invasive margin and healthy human cortical astrocytes. Liquid chromatography-mass spectrometry (LC-MS) enabled detailed analysis of biochemical pathways, and Atmospheric Pressure-Matrix Assisted Laser Desorption/Ionisation (AP-MALDI) imaging offered spatial localization of metabolites, critical for mapping their distribution within tumour microenvironments. Metabolites were extracted using a biphasic method (methanol:chloroform:water) for LC-MS analysis, and metabolic profiling was conducted using a ZIC-pHILIC column coupled with a Q-Exactive Orbitrap Mass Spectrometer. Additionally, AP-MALDI imaging facilitated the generation of high-resolution spatial distribution maps of selected metabolites, achieving a resolution of 10 µm. Both multivariate and univariate statistical analyses were applied to identify significant metabolic alterations. Metabolic profiling identified distinct pathways altered in glioblastoma cells compared to astrocytes, including alterations in aspartate, glycine and serine, and lipid metabolism. High-resolution imaging outlined the spatial distribution of metabolites involved in these pathways, revealing regions of metabolic heterogeneity. Furthermore, this methodology facilitated an expanded identification range of essential biomolecules, notably lipids and amino acids, thereby augmenting our understanding of their dynamic functions across diverse cellular contexts. By leveraging the complementary strengths of LC-MS and AP-MALDI imaging, this research enhances our understanding of spatial metabolite distribution in glioblastoma cells isolated from the invasive margin and suggests potential applications in patient tissue, offering a deeper exploration of disease mechanisms.

Cordycepin (30 deoxyadenosine) has been widely researched as a potential cancer therapy, but many diverse mechanisms of action have been proposed. Here, we confirm that cordycepin triphosphate is likely to be the active metabolite of cordycepin and that it consistently represses growth factor-induced gene expression. Bioinformatic analysis, quantitative PCR and western blotting confirmed that cordycepin blocks the PI3K/AKT/mTOR and/or MEK/ERK pathways in six cell lines and that AMPK activation is not required. The effects of cordycepin on translation through mTOR pathway repression were detectable within 30 min, indicating a rapid process. These data therefore indicate that cordycepin has a universal mechanism of action, acting as cordycepin triphosphate on an as yet unknown target molecule involved in growth factor signalling.

Plate-type fuel assembly is widely used in research reactor because of its long-term stable behavior of fuel performance and excellent thermal-mechanical behavior. KJRR (Ki-jang research reactor) fuel assembly adopted plate-type fuel which consists of U-Mo dispersed fuel meat and aluminum matrix. In structural design point of views, fuel structural integrity shall be maintained during the normal operation condition, AOOs (Anticipated operational occurrences) and non-operation conditions, and coolable geometry of fuel assembly shall be maintained during accident such as SSE (safe shutdown earthquake). Structural analyses of KJRR fuel assembly are performed considering the various structural loads expected in the reactor environment. To show that structural damage does not occur due to vibration, a flow-induced vibration test is performed in the simulated reactor loop condition. When the flow velocity is raised to sufficiently high value, fuel plates can be buckled due to unstabilizing hydrodynamic force. The measurement test of critical velocity where the buckling instability begin to occur is performed. This paper presents the structural design criteria of plate-type fuel assembly and summarizes the structural evaluation results.

Rationale: Tissue factor (TF) initiates local blood clotting and infiltration of tumor-associated macrophages, leading to tumor recurrence post-local ablation. Our study addressed inefficient cancer cell killing and immunosuppressive macrophage infiltration after percutaneous ethanol injection (PEI) in hepatocellular carcinoma (HCC). We evaluated the feasibility of ¹⁸F-radiolabeled polypeptide TF-targeted radioligand (tTF) as a PET tracer for assessing tumor response. We also explored the efficacy and safety of ¹⁷⁷Lu-radiolabeled tTF to eradicate residual tumors and tumor-associated macrophages. Methods: TF expression in the locally treated human HCC was assessed. Biodistribution, pharmacokinetics, and TF-targeted specificity of Al¹⁸F-NOTA-tTF were investigated in Kunming (KM) and/or Hepa1-6 mice. Evaluation of FDG/tTF PET imaging, histopathological characteristics, and tumor ablation response was conducted using two incomplete PEI ablation models, with ethanol volumes equivalent to 50% (high-dose (HD) PEI group) or 25% (low-dose (LD) PEI group) of the tumor volume administered. Following PEI, a single dose of ¹⁷⁷Lu-DOTA-tTF was administered on day 1 to assess its efficacy in eradicating residual tumors and immunosuppressive macrophages. Systemic toxicity was evaluated through blood analysis and histological examination of healthy organs. Results: Immunohistochemistry analysis demonstrated elevated TF expression around the ablation margin of residual tissue in human HCC. Radiolabeled tTF exhibited excellent TF-specificity, water solubility, and stability. FDG PET imaging and histological analysis showed tumor recurrence, upregulation of immunosuppressive macrophages, and TF around tumor foci post-treatment in the HD PEI-treated group. Meanwhile, the uptake of ¹⁸F-FDG exhibited a decline, while the uptake of Al¹⁸F-NOTA-tTF showed an increase in both the HD and LD PEI groups, as observed on day 1 and day 6 post-PEI. These results indicated that increased tTF uptake offers a specific and durable avenue for targeted theranostic applications. Following PEI, ¹⁷⁷Lu-DOTA-tTF therapy demonstrated significant tumor suppression and eradication of immunosuppressive macrophages compared to control groups. Safety assessments indicated no significant toxicity in the main organs of tested animals. Conclusions: Al¹⁸F-NOTA-tTF is a promising PET tracer for assessing ablated HCC, while ¹⁷⁷Lu-DOTA-tTF provides an effective tool for inhibiting residual tumor growth and immunosuppressive macrophages post-PEI. Significantly, TF-targeting theranostics may help overcome incomplete cancer cell killing and formation of tumor immunosuppressive microenvironment, offering a promising strategy for effective HCC ablation in future clinical practice.

In extreme environments people will have different needs for medicine(s), making it crucial to understand how such environments affect drug efficacy. Ibuprofen, commonly used in tablet formulation on Earth, could fail in space despite standard pharmaceutical packaging. We introduce the concept of ‘space medicines’, where solid‐dosage forms protect the pharmaceutical from accelerated degradation in spaceflight. We simulate dose(s) in International Space Station (ISS) through radionuclide and photon experiments, and establish the impact of alpha, beta and gamma rays. We demonstrate that tablet formulation protects from impact of alpha and beta rays; however, gamma rays decompose ibuprofen even when ‘masked’. We systematically analyse 19 tablet compositions inside and outside the ISS to determine the effect of compositional changes in the tablet matrix. We confirm that the iron oxide‐shielded tablets show minimal degradation (〈10%) inside the ISS, compared to moderate reductions (〉10%) for other formulations, with one exception. The tablets exhibited significantly greater ibuprofen degradation (〉 30‐50%) outside ISS, due to harsh conditions. Significantly, we found that flavour have shielding potential by scavenging free radicals. We conclude that ibuprofen efficacy is adversely affected in space, and these effects are expected to worsen on missions to deeper space destinations.