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Mutations in the breast cancer susceptibility gene 1 (BRCA1) are associated with an increased risk of breast and ovarian cancers. BRCA1 participates in the cellular DNA damage response. We report the identification of receptor-associated protein 80 (RAP80) as a BRCA1-interacting protein in humans. RAP80 contains a tandem ubiquitin-interacting motif domain, which is required for its binding with ubiquitin in vitro and its damage-induced foci formation in vivo. Moreover, RAP80 specifically recruits BRCA1 to DNA damage sites and functions with BRCA1 in G₂/M checkpoint control. Together, these results suggest the existence of a ubiquitination-dependent signaling pathway involved in the DNA damage response.

Transcription-replication conflicts lead to DNA damage and genomic instability, which are closely related to human diseases. A major source of these conflicts is the formation of R-loops, which consist of an RNA-DNA hybrid and a displaced single-stranded DNA. Although these structures have been studied, many aspects of R-loop biology and R-loop-mediated genome instability remain unclear. Here, we demonstrate that thyroid hormone receptor-associated protein 3 (Thrap3) plays a critical role in regulating R-loop resolution. In cancer cells, Thrap3 interacts with DEAD-box helicase 5 (DDX5) and localizes to R-loops. Arginine-mediated methylation of DDX5 is required for its interaction with Thrap3, and the Thrap3-DDX5 axis induces the recruitment of 5’-3’ exoribonuclease 2 (XRN2) into R-loops. Loss of Thrap3 increases R-loop accumulation and DNA damage. These findings suggest that Thrap3 mediates resistance to cell death by preventing R-loop accumulation in cancer cells. Cancer: DNA damage associated with nucleic acid loops A nuclear protein appears to inhibit cancer cell death by preventing the accumulation of nucleic acid structures called R-loops. R-loops are by-products of transcription, comprising two misaligned DNA strands and one RNA strand. They are involved in gene expression, but also threaten genome integrity and have been linked to the onset of neurodegeneration and cancers. A team led by Jang Hyun Choi and Hyug Moo Kwon, Ulsan National Institute of Science and Technology, South Korea, explored the role of Thrap3, a nuclear protein involved in RNA splicing, in R-loop-associated DNA damage. They found that Thrap3 binds to an enzyme essential for resolving R-loops. When the team suppressed Thrap3 expression, they saw an increase in R-loops in both normal and cancer cells. This R-loop accumulation significantly inhibited the growth of breast cancer cells.

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and imbalances in lipid metabolism in the liver. Although nuclear receptors (NRs) play a crucial role in hepatic lipid metabolism, the underlying mechanisms of NR regulation in NAFLD remain largely unclear. Using network analysis and RNA-seq to determine the correlation between NRs and microRNA in human NAFLD patients, we revealed that specifically targets mimic and anti- were administered to human HepG2 and Huh-7 cells and mouse primary hepatocytes as well as high-fat diet (HFD)- or methionine-deficient diet (MCD)-fed mice to verify the specific function of in NAFLD. We tested the inhibition of the therapeutic effect of a PPARα agonist, fenofibrate, by and the synergic effect of combination of fenofibrate with anti- in NAFLD mouse model. We revealed that specifically targets through miRNA regulatory network analysis of nuclear receptor genes in NAFLD. The expression of was upregulated in free fatty acid (FA)-treated hepatocytes and the livers of both obesity-induced mice and NAFLD patients. Overexpression of significantly increased hepatic lipid accumulation and triglyceride levels. Furthermore, significantly reduced FA oxidation and mitochondrial biogenesis by targeting . In -introduced mice, the effect of fenofibrate to ameliorate hepatic steatosis was significantly suppressed. Finally, inhibition of significantly increased FA oxidation and uptake, resulting in improved insulin sensitivity and a decrease in NAFLD progression. Moreover, combination of fenofibrate and anti- exhibited the synergic effect on improvement of NAFLD in MCD-fed mice. Taken together, our results demonstrate that the novel targets , plays a significant role in hepatic lipid metabolism, and present an opportunity for the development of novel therapeutics for NAFLD. This research was funded by Korea Mouse Phenotyping Project (2016M3A9D5A01952411), the National Research Foundation of Korea (NRF) grant funded by the Korea government (2020R1F1A1061267, 2018R1A5A1024340, NRF-2021R1I1A2041463, 2020R1I1A1A01074940, 2016M3C9A394589324), and the Future-leading Project Research Fund (1.210034.01) of UNIST.

The aim of this study was to elucidate the positional relationship between the courses of the angular veins and the facial muscles, and the possible roles of the latter as alternative venous valves. The angular veins of 44 specimens of embalmed Korean adult cadavers were examined. Facial muscles were studied to establish their relationships with the angular vein, including the orbicularis oculi (OOc), depressor supercilii (DS), zygomaticus minor (Zmi), zygomaticus major (Zmj), and levator labii superioris (LLS). In the upper face of all specimens, the angular vein passed through the DS and descended to the medial palpebral ligament. In the midface, it passed between the origin of the levator labii superioris alaeque nasi (LLSAN) and the inferior OOc fibers. The vein coursed along the deep surface of the inferior margin of the OOc in all specimens. At the level of the nasal ala, the course of the angular vein was classified into three types: in type I it passed between the LLS and Zmi (38.6%), in type II it passed between the superficial and deep fibers of the Zmi (47.7%), and in type III it passed between the Zmi and Zmj (13.6%). In the lower face of all specimens, the angular or facial vein passed through the anterior lobe of the buccal fat pad. This study found that the angular vein coursed along the sites where facial muscle contractions are assumed to efficiently compress the veins, likely controlling venous flow as valves. The observations made and analysis performed in this study will improve the understanding of the physiological function of the facial muscles as alternative venous valves.

Harmful algal blooms (HABs) caused by harmful cyanobacteria adversely impact the water quality in aquatic ecosystems and burden socioecological systems that are based on water utilization. Currently, Korea uses the Environmental Fluid Dynamics Code-National Institute of Environmental Research (EFDC-NIER) model to predict algae conditions and respond to algal blooms through the HAB alert system. This study aimed to establish an additional deep learning model to effectively respond to algal blooms. The prediction model is based on a deep neural network (DNN), which is a type of artificial neural network widely used for HAB prediction. By applying the synthetic minority over-sampling technique (SMOTE) to resolve the imbalance in the data, the DNN model showed improved performance during validation for predicting the number of cyanobacteria cells. The R-squared increased from 0.7 to 0.78, MAE decreased from 0.7 to 0.6, and RMSE decreased from 0.9 to 0.7, indicating an enhancement in the model’s performance. Furthermore, regarding the HAB alert levels, the R-squared increased from 0.18 to 0.79, MAE decreased from 0.2 to 0.1, and RMSE decreased from 0.3 to 0.2, indicating improved performance as well. According to the results, the constructed data-based model reasonably predicted algae conditions in the summer when algal bloom-induced damage occurs and accurately predicted the HAB alert levels for immediate decision-making. The main objective of this study was to develop a new technology for predicting and managing HABs in river environments, aiming for a sustainable future for the aquatic ecosystem.

Background Although the development of BCR::ABL1 tyrosine kinase inhibitors (TKIs) rendered chronic myeloid leukemia (CML) a manageable condition, acquisition of drug resistance during blast phase (BP) progression remains a critical challenge. Here, we reposition FLT3, one of the most frequently mutated drivers of acute myeloid leukemia (AML), as a prognostic marker and therapeutic target of BP-CML. Methods We generated FLT3 expressing BCR::ABL1 TKI-resistant CML cells and enrolled phase-specific CML patient cohort to obtain unpaired and paired serial specimens and verify the role of FLT3 signaling in BP-CML patients. We performed multi-omics approaches in animal and patient studies to demonstrate the clinical feasibility of FLT3 as a viable target of BP-CML by establishing the (1) molecular mechanisms of FLT3-driven drug resistance, (2) diagnostic methods of FLT3 protein expression and localization, (3) association between FLT3 signaling and CML prognosis, and (4) therapeutic strategies to tackle FLT3 + CML patients. Results We reposition the significance of FLT3 in the acquisition of drug resistance in BP-CML, thereby, newly classify a FLT3 + BP-CML subgroup. Mechanistically, FLT3 expression in CML cells activated the FLT3-JAK-STAT3-TAZ-TEAD-CD36 signaling pathway, which conferred resistance to a wide range of BCR::ABL1 TKIs that was independent of recurrent BCR::ABL1 mutations. Notably, FLT3 + BP-CML patients had significantly less favorable prognosis than FLT3 − patients. Remarkably, we demonstrate that repurposing FLT3 inhibitors combined with BCR::ABL1 targeted therapies or the single treatment with ponatinib alone can overcome drug resistance and promote BP-CML cell death in patient-derived FLT3 + BCR::ABL1 cells and mouse xenograft models. Conclusion Here, we reposition FLT3 as a critical determinant of CML progression via FLT3-JAK-STAT3-TAZ-TEAD-CD36 signaling pathway that promotes TKI resistance and predicts worse prognosis in BP-CML patients. Our findings open novel therapeutic opportunities that exploit the undescribed link between distinct types of malignancies. Graphical Abstract

Background: The distal oblique bundle (DOB) of the interosseous membrane (IOM) has been recognized as an important stabilizer of the distal radioulnar joint (DRUJ). However, its prevalence, morphology, and distal attachments—particularly its relationship to the articular disc and the extensor carpi ulnaris (ECU) tendon sheath—remain inconsistently described. Clarifying these anatomical details is essential for understanding DRUJ stability and guiding surgical reconstruction. Methods: The distal IOM was examined in 48 specimens from 24 embalmed Korean cadavers. In 46 dissected specimens, the presence, morphology, and attachment sites of distal interosseous structures were documented, and attachment levels were measured. In 38 specimens, attachment to the articular disc was assessed. In addition, serial transverse sections from one cadaver were analyzed to confirm three-dimensional relationships. Results: Two morphological patterns were identified: a distinct DOB (21/46, 45.7%) and, when absent, a membranous thickening of the distal IOM (25/46, 54.3%). The mean attachment level was 39.1 ± 9.7 mm for the DOB and 25.4 ± 4.8 mm for the membranous thickening. Both structures assumed an oblique orientation, fanning palmarly toward the capsule and articular disc and dorsally toward the ECU tendon sheath and dorsal septum. In 26 of 38 specimens (68.4%), these structures attached to the proximal palmar portion of the articular disc. Serial transverse sections confirmed this oblique configuration, linking palmar and dorsal stabilizers of the DRUJ. Conclusions: The distal IOM consistently forms specialized structures—either a DOB or a membranous thickening—that integrate with the triangular fibrocartilage complex. By bridging palmar and dorsal stabilizers, these structures contribute to joint congruency and load transfer during forearm rotation. A refined anatomical understanding of these patterns provides clinically relevant insights for surgical preservation or reconstruction, with the potential to improve outcomes in patients with chronic DRUJ instability.

Patients undergoing hemodialysis (HD) often experience complications, such as severe malnutrition, muscle wasting, and fluid overload, which significantly affect survival rates and quality of life. Accurate assessment and management of nutritional status and fluid retention are essential for improving patient outcomes. Bioelectrical impedance analysis (BIA), a noninvasive and practical tool, is increasingly used to assess body composition and fluid distribution in patients undergoing HD. The phase angle (PhA), a BIA parameter, reflects cellular integrity and serves as a reliable indicator of nutritional status and clinical prognosis. This review discusses the clinical utility of BIA in assessing nutritional status, fluid retention, and body composition in patients undergoing maintenance HD, with a particular focus on the PhA. The role of the PhA in predicting survival, frailty, sarcopenia, and erythropoiesis-stimulating agent resistance was explored. The application of personalized dry weight management guided by BIA has been proposed to optimize the care of patients undergoing HD. Despite limitations, including inter-device variability, lack of standardized cutoff values, and limited evidence, BIA represents a promising tool that may enhance clinical outcomes if integrated into routine clinical practice.

Autophagy functions in cellular quality control and metabolic regulation. Dysregulation of autophagy is one of the major pathogenic factors contributing to the progression of nonalcoholic fatty liver disease (NAFLD). Autophagy is involved in the breakdown of intracellular lipids and the maintenance of healthy mitochondria in NAFLD. However, the mechanisms underlying autophagy dysregulation in NAFLD remain unclear. Here, we demonstrate that the hepatic expression level of Thrap3 was significantly increased in NAFLD conditions. Liver-specific Thrap3 knockout improved lipid accumulation and metabolic properties in a high-fat diet (HFD)-induced NAFLD model. Furthermore, Thrap3 deficiency enhanced autophagy and mitochondrial function. Interestingly, Thrap3 knockout increased the cytosolic translocation of AMPK from the nucleus and enhanced its activation through physical interaction. The translocation of AMPK was regulated by direct binding with AMPK and the C-terminal domain of Thrap3. Our results indicate a role for Thrap3 in NAFLD progression and suggest that Thrap3 is a potential target for NAFLD treatment. Liver disease: Poor cellular maintenance fuels fatty liver A protein that interferes with a critical cellular housekeeping mechanism offers a promising drug target for non-alcoholic fatty liver disease (NAFLD), a condition that can lead to liver failure. Jang Hyun Choi of the Ulsan National Institute of Science and Technology, South Korea, and colleagues previously demonstrated that a protein called Thrap3 contributes to obesity-related insulin resistance. They have now investigated Thrap3 function in the liver and found that levels were significantly elevated in tissues from NAFLD patients. The researchers demonstrated that they could reduce NAFLD-associated lipid accumulation by using genetic techniques to shut down Thrap3 expression in liver cells. Thrap3 was found to inhibit autophagy, a cellular process for clearing out defective proteins and organelles. Impaired autophagy is a known contributor to NAFLD, and the authors hypothesize that Thrap3 inhibition could protect against this impairment.

Green algae play an important role in ecosystems as primary producers, but they can cause algal blooms, which are socio-environmental burdens as responding to them requires water resources from dam reservoirs. This study proposes an alternative for reducing algal blooms through dam operation without using additional water resources. A novel oscillation flow concept was suggested: oscillating discharge of dam for irregular flow. To examine its effect, the Environmental Fluid Dynamics Code—National Institute of Environment Research (EFDC-NIER) model was constructed and calibrated for the Namhan River, South Korea, from downstream of the Chungju Dam to downstream of Gangcheon Weir. The water quality in the study area were simulated and analyzed for August 2019, which is when the largest number of harmful cyanobacteria had been reported in recent years. Our results showed that the oscillation flow produced significant variance of flow velocity, and algal bloom density in the Namhan River was reduced by 20–30% through the operation of the Chungju Dam. However, further study and investigation are required before practical application.