3D epigenomics and 3D epigenopathies.

Mammalian genomes are intricately compacted to form sophisticated 3-dimensional structures within the tiny nucleus, so called 3D genome folding. Despite their shapes reminiscent of an entangled yarn, the rapid development of molecular and next-generation sequencing technologies (NGS) has revealed that mammalian genomes are highly organized in a hierarchical order that delicately affects transcription activities. An increasing amount of evidence suggests that 3D genome folding is implicated in diseases, giving us a clue on how to identify novel therapeutic approaches. In this review, we will study what 3D genome folding means in epigenetics, what types of 3D genome structures there are, how they are formed, and how the technologies have developed to explore them. We will also discuss the pathological implications of 3D genome folding. Finally, we will discuss how to leverage 3D genome folding and engineering for future studies. [BMB Reports 2024; 57(5): 216-231].

MACC1 Regulates LGR5 to Promote Cancer Stem Cell Properties in Colorectal Cancer.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. The high mortality is directly associated with metastatic disease, which is thought to be initiated by colon cancer stem cells, according to the cancer stem cell (CSC) model. Consequently, early identification of those patients who are at high risk for metastasis is crucial for improved treatment and patient outcomes. Metastasis-associated in colon cancer 1 (MACC1) is a novel prognostic biomarker for tumor progression and metastasis formation independent of tumor stage. We previously showed an involvement of MACC1 in cancer stemness in the mouse intestine of our MACC1 transgenic mouse models. However, the expression of MACC1 in human CSCs and possible implications remain elusive. Here, we explored the molecular mechanisms by which MACC1 regulates stemness and the CSC-associated invasive phenotype based on patient-derived tumor organoids (PDOs), patient-derived xenografts (PDXs) and human CRC cell lines. We showed that CD44-enriched CSCs from PDO models express significantly higher levels of MACC1 and LGR5 and display higher tumorigenicity in immunocompromised mice. Similarly, RNA sequencing performed on PDO and PDX models demonstrated significantly increased MACC1 expression in ALDH1(+) CSCs, highlighting its involvement in cancer stemness. We further showed the correlation of MACC1 with the CSC markers CD44, NANOG and LGR5 in PDO models as well as established cell lines. Additionally, MACC1 increased stem cell gene expression, clonogenicity and sphere formation. Strikingly, we showed that MACC1 binds as a transcription factor to the LGR5 gene promoter, uncovering the long-known CSC marker LGR5 as a novel essential signaling mediator employed by MACC1 to induce CSC-like properties in human CRC patients. Our in vitro findings were further substantiated by a significant positive correlation of MACC1 with LGR5 in CRC cell lines as well as CRC patient tumors. Taken together, this study indicates that the metastasis inducer MACC1 acts as a cancer stem cell-associated marker. Interventional approaches targeting MACC1 would potentially improve further targeted therapies for colorectal cancer patients to eradicate CSCs and prevent cancer recurrence and distant metastasis formation.

Development of Nano-Sized Copper-Deposited Antimicrobial Air Filters Using a Mixed Melt-Blown Process.

Air purification devices, such as air purifiers, provide fresh air by filtering out airborne pollutants, dust, and other harmful substances using various filter systems. While air filters are generally effective in filtering pollutants such as dust, they encounter a challenge when filtering harmful microorganisms such as mites, bacteria, mold, and viruses. These microorganisms, which are present in public transport and public indoor spaces, tend to proliferate on the surface of the filter media, eventually reintroducing themselves into the air or causing unpleasant odors. To address this issue, herein, copper particles were prepared as one masterbatch and deposited on polypropylene (PP) pellets through plasma vacuum deposition to effectively filter dust and microorganisms and prevent their growth on the surface of the filter media. After adding 3-10 wt.% of the masterbatch to conventional PP pellets to fabricate a filter media, the distribution of copper on the surface of the filter media was observed through a scanning electron microscope. To verify the safety and effectiveness of the antimicrobial material, the filter media containing antimicrobial particles was tested using Escherichia coli (E. coli) and Staphylococcus aureus through a filter emission test.

Deep-Learning-Based Emergency Stop Prediction for Robotic Lower-Limb Rehabilitation Training Systems.

Robotic lower-limb rehabilitation training is a better alternative for the physical training efforts of a therapist due to advantages, such as intensive repetitive motions, economical therapy, and quantitative assessment of the level of motor recovery through the measurement of force and movement patterns. However, in actual robotic rehabilitation training, emergency stops occur frequently to prevent injury to patients. However, frequent stopping is a waste of time and resources of both therapists and patients. Therefore, early detection of emergency stops in real-time is essential to take appropriate actions. In this paper, we propose a novel deep-learning-based technique for detecting emergency stops as early as possible. First, a bidirectional long short-term memory prediction model was trained using only the normal joint data collected from a real robotic training system. Next, a real-time threshold-based algorithm was developed with cumulative error. The experimental results revealed a precision of 0.94, recall of 0.93, and F1 score of 0.93. Additionally, it was observed that the prediction model was robust for variations in measurement noise.

The difference of in-shoe plantar pressure between level walking and stair walking in healthy males.

Stair walking is more demanding locomotion than level walking and can aggravate discomfort of the foot. The purpose of this study is to analyze plantar pressure distribution and pressure patterns during gait cycle at stair walking compared to level walking. Thirty-five healthy males with 23.4 ± 2 years old were included in this study after examining normality. They performed level walking, stair ascending, and descending in same type of shoes. Measurements of in-shoe plantar pressure including peak pressure, pressure-time integral were done by Pedar-X system, masked 7 regions. Also, pressures in each region throughout the gait cycle were analyzed from each type of walking. Statistical analysis was performed using repeated measure one way analysis of variance. Peak pressure in all regions except for the midfoot was higher during level walking than stair walking. Pressure-time integral in the forefoot, midfoot during stair ascending, and the forefoot during stair descending was higher than level walking. In gait cycle, first peak was produced in the heel and the second peak was produced in the hallux during level walking, whereas during stair ascent, the heel and midfoot were in first peak, and the second peak was in the hallux. During stair descent, the first peak were in the forefoot and the midfoot, and the second peak was in the forefoot. In healthy young male adults, forefoot and midfoot are significant regions in the way that they have higher pressure burdens than other foot regions during stair walking.

Study of mutagenicities of phthalic acid and terephthalic acid using in vitro and in vivo genotoxicity tests.

Genotoxicities of phthalic acid (PA) and terephthalic acid (TPA) were examined using three mutagenicity tests: Ames, chromosome aberration (CA), and micronucleus (MN). In the Ames test, these two agents did not produce any mutagenic responses in the absence or presence of S9 mix on the Salmonella typhimurium strains TA98, TA100, TA102, TA1535, or TA1537. The CA test also showed that PA and TPA exerted no significant cytogenetic effect on Chinese hamster ovary (CHO) cells. In the mouse MN test, no significant alteration in occurrence of micronucleated polychromatic erythrocytes was observed in ICR male mice ip administered any of these agents at doses of 0, 20, 100, 500, 2500 or 12,500 microM/kg. These results indicate that PA and TPA produced no mutagenic effects using these in vitro and in vivo mutagenic test systems.

Evaluation of the genotoxicity of (-)-hydroxycitric acid (HCA-SX) isolated from Garcinia cambogia.

(-)-Hydroxycitric acid (HCA) is widely used as an ingredient for nutritional supplements aimed at reducing food intake, appetite, and body weight. In this study, the genotoxicity of HCA was evaluated using three tests: a bacterial reverse mutation assay (Ames test), an in vitro chromosomal aberration (CA) test, and an in vivo micronucleus (MN) test. HCA was negative by the Ames test in the presence or absence of a microsomal metabolizing system. HCA did not induce mutagenic activity in the Ames test, and no significant mutagenic potency was indicated by CA tests. However, HCA significantly and dose-dependently increased the number of MNPCEs (micronucleated polychromatic erythrocytes/1000 polychromatic erythrocytes) and PCE/(PCE + NCE) ratios according to the MN test. These results suggest that HCA preferentially induce micronuclei.

Design Principle and Loss Engineering for Photovoltaic-Electrolysis Cell System.

The effects of exchange current density, Tafel slope, system resistance, electrode area, light intensity, and solar cell efficiency were systematically decoupled at the converter-assisted photovoltaic-water electrolysis system. This allows key determinants of overall efficiency to be identified. On the basis of this model, 26.5% single-junction GaAs solar cell was combined with a membrane-electrode-assembled electrolysis cell (EC) using the dc/dc converting technology. As a result, we have achieved a solar-to-hydrogen conversion efficiency of 20.6% on a prototype scale and demonstrated light intensity tracking optimization to maintain high efficiency. We believe that this study will provide design principles for combining solar cells, ECs, and new catalysts and can be generalized to other solar conversion chemical devices while minimizing their power loss during the conversion of electrical energy into fuel.

Neutrophil extracellular traps (NETs) in autoimmune diseases: A comprehensive review.

Neutrophil extracellular traps (NETs) are fibrous networks which protrude from the membranes of activated neutrophils. NETs are found in a variety of conditions such as infection, malignancy, atherosclerosis, and autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), psoriasis, and gout. Studies suggest that an imbalance between "NETosis," which is a process by which NETs are formed, and NET degradation may be associated with autoimmune diseases. Neutrophils, interleukin-8, ANCA and other inflammatory molecules are considered to play a key role in NET formation. Prolonged exposure to NETs-related cascades is associated with autoimmunity and increases the chance of systemic organ damage. In this review, we discuss the roles of various inflammatory molecules in relation to NETs. We also describe the role of NETs in the pathogenesis of autoimmune diseases and discuss the possibility of using targeted therapies directed to NETs and associated molecules to treat autoimmune diseases.

Morphological Characteristics of Ginseng Leaves in High-Temperature Injury Resistant and Susceptible Lines of Panax ginseng Meyer.

Plant leaf cuticle is related to the prevention of moisture loss, transpiration, and diffusion of light reflection. The purpose of this study was to examine the morphological characteristics of ginseng leaves in ginseng plants resistant and susceptible to high temperature injury (HTI) to be related with the leaf-burning. For the HTI resistant lines Yunpoong, high-temperature injury resistance (HTIR) 1, HTIR 2, and HTIR 3, and the HTI-susceptible line Chunpoong, the cuticle densities were 53.0%, 46.2%, 44.9%, 48.0%, and 17.0%; the adaxial leaf cuticle layers were 141.3, 119.7, 119.7, 159.4, and 85.0 nm in thickness; the abaxial leaf cuticle layers were 153.6, 165.8, 157.9, 199.6, and 119.4 nm in thickness; and the stomtal lengths were 21.7, 32.4, 29.4, 30.9, and 21.8 µm, respectively. All of these aspects suggest that HTI resistant lines have higher cuticle density, thicker adaxial and abaxial leaf cuticle layers, and longer of stomta length than the HTI-susceptible line, protecting leaves from moisture loss and excessive transpiration under high temperatures to be resistant against the leaf-burning.