Chonnam National University

Biomaterial composition and surface charge play a critical role in macrophage polarization, providing a molecular cue for immunomodulation and tissue regeneration. In this study, we developed bifunctional hydrogel inks for accelerating M2 macrophage polarization and exosome (Exo) cultivation for wound healing applications. For this, we first fabricated polyamine-modified three-dimensional (3D) printable hydrogels consisting of algi-nate/gelatin/polydopamine nanospheres (AG/NSPs) to boost M2-exosome (M2-Exo) secretion. The cultivated M2-Exo were finally encapsulated into a biocompatible collagen/decellularized extracellular matrix (COL@d-ECM) bioink for studying angiogenesis and in vivo wound healing study. Our findings show that 3D-printed AGP hydrogel promoted M2 macrophage polarization by Janus kinase/signal transducer of activation (JAK/STAT), peroxisome proliferator-activated receptor (PPAR) signaling pathways and facilitated the M2-Exo secretion. Moreover, the COL@d-ECM/M2-Exo was found to be biocompatible with skin cells. Transcriptomic (RNA-Seq) and real-time PCR (qRT-PCR) study revealed that co-culture of fibroblast/keratinocyte/stem cells/endothelial cells in a 3D bioprinted COL@d-ECM/M2-Exo hydrogel upregulated the skin-associated signature biomarkers through various regulatory pathways during epidermis remodeling and downregulated the mitogen-activated protein kinase (MAPK) signaling pathway after 7 days. In a subcutaneous wound model, the 3D bioprinted COL@d-ECM/M2-Exo hydrogel displayed robust wound remodeling and hair follicle (HF) induction while reducing canonical pro-inflammatory activation after 14 days, presenting a viable therapeutic strategy for skin-related disorders.

The SENORITA phase III trial demonstrated the effectiveness of laparoscopic sentinel node navigation surgery (LSNNS) in preserving stomach function for patients with early gastric cancer (EGC), although some patients experienced surgical failure or recurrence. The purpose of this study was to analyze patients’ clinicopathologic features from the SENORITA trial who were allocated to LSNNS with stomach-preserving surgery but ultimately did not preserve stomach or experienced recurrence. Patients were categorized into two groups: the failure group (stomach preservation failure or cancer recurrence after LSNNS) and the success group (stomach preservation without recurrence following LSNNS). This study analyzed the detailed clinicopathologic characteristics of patients in the failure group from the SENORITA trial. Among 258 patients who underwent LSNNS, 193 patients (74.8%) achieved stomach preservation, while 65 patients (25.2%) failed to preserve. Intraoperative failure was the most common cause of unsuccessful stomach preservation, occurring in 35 of 65 cases (53.8%). Advanced pathological TNM stage was the only independent risk factor by multivariate analysis, with stage IB and IIA patients showing 5.9- and 45.0-fold higher failure risks. The main causes of failure included sentinel basin detection failure, metastatic lymph nodes, positive tumors at resection margins, and complications. The failure group also included five cases of gastric cancer recurrence following LSNNS. Accurate preoperative staging and patient selection are crucial for optimizing LSNNS outcomes. Ensuring precise resection with an adequate number of harvested sentinel basin nodes is essential to succeed the stomach-preserving surgery.

Background Cancer immunotherapy, leveraging the immune system to target and eradicate cancer cells, has transformed cancer treatment paradigms. Immune checkpoint inhibitors (ICIs) are used in a wide array of cancers, but only a limited fraction of patients are responding. Cancer vaccines could elicit antigen-specific immune responses and establish long-term immune memory, preventing recurrence and metastasis. Despite their promising profiles, ICIs and cancer vaccines by themselves are often insufficient to overcome the immunosuppressive tumor microenvironment (TME) and recurrence/metastasis. Addressing these challenges is crucial for improving cancer immunotherapy outcomes. Methods The targeted liposomal formulation (TLIF), displaying Cyclic RGD (cRGD) peptide on the surface and encapsulating ICG and thermoresistant flagellin (FlaB) inside, was used for photothermal therapy (PTT), which was designed to induce robust immunogenic cell death (ICD) and release tumor antigens (TAs). We employed a mouse breast cancer model amenable to PTT. Utilizing a bilateral DD-Her2/neu tumor implantation model, we evaluated local and abscopal effects of combinatorial approaches employing PTT, FlaB-adjuvanted peptide vaccine (FlaB-Vax), and anti-PD-1 treatment. FlaB-Vax was designed to trigger tumor-associated antigen (TAA)-specific immune responses, which will trigger specific anti-tumor immunity. TLIF-PTT aimed to reduce tumor burden and induce ICD-mediated TA liberation for epitope spreading. Sustained anti-tumor immune memory was assessed by orthotopic rechallenging cured mice with the DD-Her2/neu tumor cells. Results The combination of TLIF-PTT and FlaB-Vax provided significantly enhanced primary tumor suppression, with strong abscopal effects and long-lasting immune memory. The addition of anti-PD-1 therapy further improved long-term relapse-free survival, highlighting the potential of this combinatorial approach to induce durable antitumor immunity and sustainably prevent cancer recurrence and metastasis. Conclusion This study demonstrates that the combination of TLIF-PTT and FlaB-Vax synergistically induced synergistic anti-tumor immune responses, which were efficaciously potentiated by anti-PD-1 treatment for recurrence-free long-term survival.

Despite the great potential of photodynamic therapy (PDT), its success remains compromised by the abnormal redox homeostasis of tumor cells, which supports survival, growth, and resistance to oxidative therapeutic interventions by neutralizing reactive oxygen species (ROS). To overcome this barrier, a multifunctional prodrug nanomodulator (Pro@FLNC) is designed to induce disulfidptosis and immunogenic pyroptosis to trigger an antitumor immune response. Pro@FLNC features a prodrug core–shell structure where ursolic acid (UA) and Chlorin e6 (Ce6) are conjugated via a GSH‐responsive linker and encapsulated in a DSPE‐PEG‐FA lipid shell for enhanced stability, biocompatibility, and tumor‐specific targeting. Within the tumor microenvironment (TME), Pro@FLNC depletes intracellular GSH, disrupts redox homeostasis, and releases Ce6 and UA, triggering oxidative stress and mitochondrial dysfunction. These mechanisms amplify ROS production, promote lipid peroxidation, and initiate disulfidptosis, evidenced by increased SLC7A11 expression and F‐actin collapse. Elevated ROS levels and metabolic imbalance‐triggered disulfidptosis further activate immunogenic pyroptosis, releasing damage‐associated molecular patterns (DAMPs) that stimulate dendritic cell maturation and cytotoxic T‐cell activation. Together, Pro@FLNC reshapes the TME, reduces immunosuppressive cells, and promotes CD8⁺ T‐cell infiltration, effectively suppressing primary tumors and metastases. This programmed prodrug nanomodulator offers a promising strategy to enhance PDT and immunotherapy for advanced breast cancer.

Omega-3 fatty acids (O3FA) and statins effectively reducing the levels of triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), respectively, and are actively used in clinical practice worldwide for the treatment of hyperlipidemia. Combinations of O3FA and statins have been found effective in managing complex dyslipidemia cases and achieving synergistic therapeutic effects while improving patient compliance. This study was conducted to examine the current status of the development of combinations of O3FA and statins, which have recently been garnering attention, and to consider future approaches to developing additional formulations. By reviewing published literature and market reports, we summarize the development status of O3FA and statin combinations. We also identified a scope for improvement in such formulations and propose new formulation development approaches. Co-administration of direct physical combinations of O3FA and statins is generally considered safe and free of drug interactions, but inherent challenges to drug stability exist. In particular, O3FA oxidation is highly possible, necessitating a spatially separated combination technology without direct contact with statins. An attempt to encapsulate O3FA within soft capsules and statin drugs as powders, granules, or tablets in a hollow capsule was proposed as a new approach that can solve both the stability issues due to potential interactions between ingredients and the content change issues due to ingredient loss during mechanical transport. In addition, a novel combination formulation with fibrate or ezetimibe was proposed to improve TG, cholesterol, and LDL-C levels while maximizing compliance in patients taking multiple medications. Attempts to formulate combinations of anti-hyperlipidemic drugs are becoming popular in the management of complex dyslipidemia cases. In this context, this study presents important pharmaceutical perspectives on combining O3FA and statins. The findings presented herein provide useful insights into developing additional improved oral formulations in the future.

Pine wilt disease (PWD) is a devastating disease caused by the pinewood nematode (Bursaphelenchus xylophilus). Its substantial ecological disruption harms global forestry and poses serious economic challenges. Although previous research has demonstrated that Bacillus subtilis JCK-1398 has the potential to induce systemic resistance in pine trees, the ecological mechanisms underlying its biocontrol efficacy remain underexplored. This study investigated how JCK-1398 treatment influences rhizosphere- and nematode-associated microbial communities to mitigate PWD. Metabarcoding analyses revealed that JCK-1398 treatment increased the abundance of beneficial microbial taxa (e.g., Nocardioides and Mesorhizobium) in the rhizosphere microbiome. Concurrently, nematode-associated microbial communities became dominated by Pantoea, a genus with known nematicidal properties. Isolation and characterization of Pantoea dispersa BC11 confirmed that it significantly limits nematode viability. These findings highlight the multifaceted defense that JCK-1398 offers, not only inducing systemic resistance, but also orchestrating beneficial microbiome dynamics. This study emphasizes the potential of manipulating a microbial holobiont for eco-friendly and sustainable disease management. The ability of JCK-1398 to recruit and enhance microbial allies offers a novel framework for developing biocontrol agents, with implications for managing PWD and other plant-pathogen systems.

Multiple enzymatic biotransformation of methanol into ethanolamine via formaldehyde and glycolaldehyde was investigated. After discovery of an amine transaminase (ATA), the transamination reaction was connected to condensation of formaldehyde into glycolaldehyde. The ATA from Silicibacter pomeroyi (SpATA), which showed broad substrate spectrum from C4 to C14 aliphatic aldehydes, was able to catalyze the transamination of glycolaldehyde into ethanolamine. The kinetic studies revealed that KM, kcat, and kcat/KM values for glycolaldehyde were 4.3 mM, 2.4 s−1, and 0.56 mM−1 s−1, respectively. The cascade transformation of methanol into ethanolamine via formaldehyde and glycolaldehyde by the isolated alcohol oxidase from Hypoxylon sp., glyoxylate carboligase from Escherichia coli, and the recombinant E. coli cells expressing the SpATA led to production of ethanolamine to a bioconversion of 42%. This study will contribute to valorization of C1 chemicals into industrially relevant multi-carbon products.

Objectives This study aimed to establish updated diagnostic reference levels (DRLs) for dental imaging modalities in South Korea. Methods In cooperation with the Korea Disease Control and Prevention Agency, various types of institutions (dental clinics, dental hospitals, and dental university hospitals) were selected to investigate the status of diagnostic radiation equipment use. Subsequently, over 300 units were randomly selected for each imaging device type (intraoral, panoramic, and cone-beam CT [CBCT]) as measurement samples. DRLs were defined as the 75th percentile of the dose area product distribution. The differences in dose were analysed based on the type of institution, age of use, country of manufacture, and presence of a multifunction device. Results The national DRLs for dental imaging established in this survey were as follows: intraoral imaging at 48 mGy·cm2 for adults and 31 mGy·cm2 for children; panoramic imaging at 354 mGy·cm2 for adults and 224 mGy·cm2 for children; and CBCT at 1856 mGy·cm2 for adults and 1350 mGy·cm2 for children. Private dental clinics and hospitals recorded approximately twice the dose levels of university dental hospitals. CBCT devices in dental hospitals and those that have been in used for 5-10 years showed significantly high radiation doses. Conclusions The DRLs established through this study were found to be significantly increased, especially in adult and paediatric panoramic radiographs and paediatric CBCT images, compared with those in previous surveys; moreover, they were higher than those in other countries. The findings of this study can serve as a basis for national dose reduction efforts.

This study investigates the impact of the transition from viscous linear to inertial nonlinear flows on solute mixing and partitioning at rough‐walled fracture intersections, using direct observations of flow dynamics and solute partitioning processes through microscopic particle image velocimetry. It is generally known that mixing at fracture intersections decreases when transport shifts from diffusion‐dominated to advection‐dominated processes, but this trend holds only in viscous linear flows. The experimental results conducted in this study reveal that in inertial flows, significant changes in flow structures occur at rough‐walled fracture intersections, including the straightening and stretching of main streamlines and the formation of fully developed eddies. Fluid stretching and the formation of eddies contribute to advection‐driven diffusive mixing. The straightened streamlines deliver solutes to the outflow leg along a direct path. More importantly, fully developed eddies generate spiral advective paths that reconnect to the main flow channels, enhancing solute redistribution at the intersection. Microscopic measurements and quantitative analyses show that flow nonlinearity—including the formation of eddies, along with enhanced flow straightening and stretching—contributes to increased flow heterogeneity and solute redistribution at fracture intersections. This phenomenon appears as an increase in “apparent” mixing at rough‐walled fracture intersections.

Herein, the strategy of homogenous inclusion of nanoparticles within the surface and interlayers of 2D MXenes was established to achieve effective OER performance. A greater quantity of ~6 nm sized Ni(OH)2 particles uniformly anchored on multi‐layered accordion‐like nanosheets of Ti3C2Tx. The strong interconnection of Ni(OH)2 on Ti3C2Tx promoting synergistic effects and improves electron transfer properties alongside the intrinsic OER activity. The Ti3C2Tx‐Ni(OH)2‐4 demonstrated remarkable OER activity by exhibiting a lower overpotential (235.54 mV at 10 mA/cm2) in alkaline conditions. Increased ECSA (2.925 mF cm‐2), lower charge transfer resistance, lowering the reaction barrier and stabilizing/converting essential intermediates via the Ti3C2Tx‐Ni(OH)2 electrocatalyst synergistically improve OER activity. The effective interaction between Ti3C2Tx and Ni(OH)2 in Ti3C2Tx‐Ni(OH)2 improves stability during long‐term operations. Moreover, a Ti3C2Tx‐Ni(OH)2‐4||Pt/C cell has 1.7V at 10 mA/cm2. It could be deduced that the usage of Ni(OH)2 as an electrocatalyst together with Ti3C2Tx can provide noteworthy water splitting properties.

Background Alzheimer's disease (AD) is characterized by a gradual synaptic loss. The progression of AD severely affects late‐phase long‐term potentiation (L‐LTP), which is essential for long‐term memory consolidation. Aim We have previously demonstrated the beneficial effects of acute restraint stress (ARS) on hippocampal LTP in AD mouse models. This study aimed to verify the effects and potential mechanisms of ARS on the maintenance of hippocampal L‐LTP in two AD mouse models. Materials and Methods 5xFAD and Tg2576 mice underwent a 30‐min body immobilization protocol to induce ARS, followed by electrophysiological recordings of L‐LTP (> 3 h) in the CA1 region of thehippocampus. Results The ARS‐exposed group exhibited significantly enhanced L‐LTP compared to the control group. Maintenance of L‐LTP requires new protein synthesis and signaling via the mammalian target of rapamycin (mTOR) pathway. Our findings revealed that ARS increased hippocampal adenosine triphosphate (ATP) production and reduced AMPK activity. Inactivation of AMPK and subsequent activation of the mTOR pathway were strongly associated with the ARS‐facilitated enhancement of L‐LTP. Furthermore, our experiments using the mTOR inhibitor rapamycin demonstrated that it effectively prevented the enhancement of L‐LTP following ARS, underscoring the pivotal role of mTOR in this process. Conclusion ARS may significantly modify AMPK activation and mTOR regulation in L‐LTP, potentially triggering the mechanisms of long‐term memory consolidation in AD mouse model mice. Identifying these underlying mechanisms could help promote the development of novel pharmaceutical agents for the treatment of AD.

Early detection of amyotrophic lateral sclerosis (ALS) progression is critical for improving disease management and therapeutic outcomes. However, the clinical heterogeneity and variability in ALS symptoms often lead to delayed diagnosis and suboptimal therapeutic interventions. Since mitochondrial dysfunction is a hallmark of ALS, we hypothesized that monitoring mitochondrial function could serve as a reliable strategy for early diagnosis and therapeutic monitoring of ALS. To address this, we synthesized and characterized 2 novel near-infrared fluorophores, ALS04 and ALS05, designed to target mitochondria and lysosomes. Their physicochemical properties, serum protein binding, fluorescence characteristics, photostability, and pharmacokinetics were systematically evaluated. We found that benzothiazole-based fluorophores exhibit excellent mitochondrial targeting, optimal optical properties, biocompatibility, and favorable biodistribution in vivo. Interestingly, ALS04 showed superior mitochondrial accumulation compared to ALS05, despite their similar physicochemical properties. This enhanced accumulation can be attributed to the lower molecular weight and higher lipophilicity of ALS04. Real-time fluorescence imaging revealed a substantial reduction in ALS04 signals in mitochondrial-rich tissues such as brown fat, highlighting its potential for monitoring mitochondrial dysfunction in early-stage ALS. Furthermore, the detection of ALS04 in the mouse brain suggests its ability to monitor blood–brain barrier hyperpermeability, another key feature of ALS pathology. These findings establish ALS04 as a promising noninvasive imaging tool for monitoring biomarkers associated with ALS progression. Its ability to detect early-stage pathophysiological changes in an ALS mouse model highlights its potential for advancing our understanding of ALS mechanisms and facilitating the identification of novel therapeutic targets.

Ticks are well‐known vectors of various diseases and are widely distributed globally. In this study, we investigated the microbial community of Haemaphysalis flava , a common tick species in Korea, using 16S rRNA gene analysis. Alpha diversity analysis revealed that adult ticks had higher microbial richness and complexity than nymphs, and the highest diversity was observed in adult females. Significant regional differences were also found, with samples from Jinju and Boseong showing higher richness and samples from Jeju showing lower richness. Beta diversity analysis showed that microbial communities were clustered according to region and developmental stage, with unique clusters observed in Samcheok and Gokseong, which may be due to regional environmental factors. Proteobacteria dominated the microbial community in most samples, followed by Actinobacteriota and Firmicutes. At the genus level, Coxiella and Pseudomonas were dominant, and Coxiella may be associated with pathogen transmission. The abundance of other genera varied by region and developmental stage, reflecting complex host–microbe interactions. These findings highlight the influence of environmental, developmental, and biological factors on the H. flava microbiota, emphasizing the need for further research to understand the ecological role of the microbiota in pathogen transmission and to develop effective strategies for preventing tick‐borne diseases.

Early detection of wasp hives is crucial for mitigating their impact on native species, preventing agricultural damage, and improving pest control strategies. Traditional detection methods rely on ground surveys and sensor‐based tracking of individual insects, which are often labor‐intensive, time‐consuming, and prone to errors because of environmental constraints. The integration of artificial intelligence and drone‐based imaging has the potential to revolutionize ecological monitoring by providing scalable, efficient, and noninvasive methods for detecting wasp hives. However, research on AI‐assisted hive detection remains limited, with most studies focusing on large‐scale wildlife monitoring rather than small‐object localization. Therefore, we propose a system for searching the candidate site of a wasp hive using a small drone. In the proposed system, a small drone is equipped with a camera and takes aerial images of the error range. Subsequently, three‐dimensional (3D) modeling is performed on the captured images using a 3D surveying toolkit, and deep learning–based hive detection is performed on the completed 3D model to extract the GPS information of the detected target.