Gyeongsang National University

A R T I C L E I N F O Keywords: Parkinson's disease α-Synuclein α-Syn peptide Autoimmune response T cell Neuronal cell death Glial cell activation A B S T R A C T Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the loss of dopaminergic neurons and neuroinflammation. Recent studies have identified a role of T cells in the pathogenesis of PD. Additionally, these studies suggested that α-synuclein (α-Syn) is related to abnormal T-cell responses and may act as an epitope and trigger autoimmune T-cell responses. However, it is unclear whether the α-Syn-mediated autoimmune response occurs and whether it is related to neuronal cell death and glial cell activation. In this study, we investigated the autoimmune T-cell response induced by α-Syn peptides and evaluated the neurotoxic effect of the α-Syn peptide-mediated autoimmune response. The immunization of mice with α-Syn peptides resulted in enhanced autoimmune responses, such as the peptide recall response, polarization toward Th1/Th17 cells, and regulatory T cell imbalance. Furthermore, the α-Syn autoimmune response led to the death of primary neurons cocultured with splenocytes. Treatment with conditioned media from α-Syn peptide-immunized sple-nocytes induced microglia and toxic A1-type astrocyte activation. Taken together, our results provide evidence of the potential role of the α-Syn-initiated autoimmune response and its contribution to neuronal cell death and glial cell activation.

Background and Aims Platelet-fibrin clot strength (PFCS) is linked to major adverse cardiovascular event (MACE) risk. However, the association between PFCS and platelet reactivity and their prognostic implication remains uncertain in patients undergoing percutaneous coronary intervention (PCI). Methods In PCI-treated patients (n = 2512) from registry data from January 2010 to November 2018 in South Korea, PFCS using thromboelastography and platelet reactivity using VerifyNow were measured. High PFCS (PFCSHigh) was defined as thromboelastography maximal amplitude ≥ 68 mm, and high platelet reactivity (HPR) was defined as >208 P2Y12 reaction units. Patients were stratified into four groups according to maximal amplitude and P2Y12 reaction unit levels: (i) normal platelet reactivity (NPR)-PFCSNormal (31.8%), (ii) HPR-PFCSNormal (29.0%), (iii) NPR-PFCSHigh (18.1%), and (iv) HPR-PFCSHigh (21.1%). Major adverse cardiovascular event (all-cause death, myocardial infarction, or stroke) and major bleeding were followed up to 4 years. Results High platelet reactivity and PFCSHigh showed an additive effect for clinical outcomes (log-rank test, P < .001). Individuals with NPR-PFCSNormal, NPR-PFCSHigh, HPR-PFCSNormal, and HPR-PFCSHigh demonstrated MACE incidences of 7.5%, 12.6%, 13.4%, and 19.3%, respectively. The HPR-PFCSHigh group showed significantly higher risks of MACE compared with the NPR-PFCSNormal group [adjusted hazard ratio (HRadj) 1.89; 95% confidence interval (CI) 1.23–2.91; P = .004] and the HPR-PFCSNormal group (HRadj 1.60; 95% CI 1.12–2.27; P = .009). Similar results were observed for all-cause death. Compared with HPR-PFCSNormal phenotype, NPR-PFCSNormal phenotype was associated with a higher risk of major bleeding (HRadj 3.12; 95% CI 1.30–7.69; P = .010). Conclusions In PCI patients, PFCS and platelet reactivity demonstrated important relationships in predicting clinical prognosis. Their combined assessment may enhance post-PCI risk stratification for personalized antithrombotic therapy.

Atherosclerosis is a cardiovascular disease mainly caused by plaque deposition in blood vessels. Plaque comprises components such as thrombosis, fibrin, collagen, and lipid core. It plays an essential role in inducing rupture in a blood vessel. Generally, Plaque could be described as three kinds of elastic models: cellular Plaque, hypocellular Plaque, and calcified Plaque. The present study aimed to investigate the behavior of atherosclerotic plaque rupture according to different lipid cores using Fluid-Structure Interaction (FSI). The blood vessel was also varied with different thicknesses (0.05, 0.25, and 0.5 mm). In this study, FSI simulation with a cellular plaque model with various thicknesses was investigated to obtain information on plaque rupture. Results revealed that the blood vessel with Plaque having a lipid core represents higher stresses than those without a lipid core. Blood vessels' thin thickness, like a thin cap, results in more considerable than Von Mises stress. The result also suggests that even at low fracture stress, the risk of rupture due to platelet decomposition at the gap was more significant for cellular plaques.

Background Human fishing activities have significantly affect environmental concern for marine ecosystems, conservation of marine mammals, and human health. Coastal cetaceans are highly vulnerable to ingestion of fishing gear, bycatching, or entanglement, all of which can be fatal for these animals. In particular, certain coastal dolphins and porpoises are heavily impacted by fishing gear such as angling gear or stownet, as their food often overlap with the target fish species of human fisheries. Case presentation This study presents a case of an Indo-Pacific finless porpoise (Neophocaena phocaenoides) beached on the coast of Jeju Island, Republic of Korea, with ingestion of fishing gear and severe Anisakis infection. Although this species inhabits waters ranging from the Persian Gulf to Taiwan, several stranded carcasses have been reported on Jeju Island in recent years. Post-mortem computed tomography revealed a bundle of four fishing hooks in the forestomach, along with nylon lines and steel lines with connectors, which were assumed to be angling gear for Jeju hairtail (Trichiurus lepturus). Further necroscopic investigation revealed that the forestomach contained a large number of Anisakis spp. (Nematoda: Anisakidae). Histological examination revealed a thickened forestomach wall with pinpoint and volcanic ulcerations, a thickened layer of stratified squamous epithelium, and infiltrated stroma in the squamous epithelium. Conclusions This study emphasizes the urgent need to address the impact of fishing activities on marine mammals, marine litter pollution, and the bycatch problem in Korean seawater. In addition, the occurrence of N. phocaenoides in seawater around Jeju Island should be raised in future geographical ecology or veterinary pathology studies and when its distribution is updated.

Despite their outstanding safety, longevity, environmental friendliness, and high energy storage capabilities, the deterioration and damage of the Zn anode of Zn-ion batteries (ZIBs), their inadequate wettability, and a lack of sufficient nucleation points for Zn plating have hindered the further development of ZIBs. Thus, research efforts are focused on improving safety by coating Zn anodes with protective materials, such as carbon, ceramics, or polymers. This study coated the surface of Zn anode with a protective composite consisting of poly(vinylidene fluoride) (PVDF) and carbon nanotubes (CNTs) to protect it and improve its electrochemical performance. The PVDF coating functioned as an effective barrier against Zn dissolution and corrosion, while the CNTs enriched the anode with abundant sites for Zn deposition and significantly diminished the surface resistance of the electrode. The ZIB fabricated using the coated Zn anode exhibited an enhanced specific capacity of 253 mA h g–1 at 0.3 A g–1, maintaining a specific capacity of 91 mA h g–1 over 500 cycles at 0.5 A g–1. The results suggest that employing a composite protective layer made of PVDF and CNT is a promising method for enhancing the energy storage potential of ZIBs.

Plasmodesmata (PDs) are intercellular organelles carrying multiple membranous nanochannels that allow the trafficking of cellular signalling molecules. The channel regulation of PDs occurs dynamically and is required in various developmental and physiological processes. It is well known that callose is a critical component in regulating PD permeability or symplasmic connectivity, but the understanding of the signalling pathways and mechanisms of its regulation is limited. Here, we used the reverse genetic approach to investigate the role of C‐type lectin receptor‐like kinase 1 (CLRLK1) in the aspect of PD callose‐modulated symplasmic continuity. Here, we found that loss‐of‐function mutations in CLRLK1 resulted in excessive PD callose deposits and reduced symplasmic continuity, resulting in an accelerated gravitropic response. The protein interactome study also found that CLRLK1 interacted with actin depolymerizing factor 3 (ADF3) in vitro and in plants. Moreover, mutations in ADF3 result in elevated PD callose deposits and faster gravitropic response. Our results indicate that CLRLK1 and ADF3 negatively regulate PD callose accumulation, contributing to fine‐tuning symplasmic opening apertures. Overall, our studies identified two key components involved in the deposits of PD callose and provided new insights into how symplasmic connectivity is maintained by the control of PD callose homoeostasis.

Numerical simulations provide an improved understanding of the evolution and core formation processes of terrestrial bodies. The differentiation of silicate and iron metal has been simulated by solving the two-dimensional Stokes equation using either the vector or potential method. To describe the realistic geometry of planetesimals and planets, the development of a 3D model is necessary. Here, we developed a vector method model implemented in FEniCS project via scripting the weak forms of governing equations. Subsequently, we compared the solutions of the vector method models with those of the benchmark potential method implemented in Python. Three cases were modeled using the two methods and confirmed for consistency to verify the feasibility of developing a 3D model for core formation. Case 1 corresponds to planetary evolution triggered by impact heating in early terrestrial bodies with a homogeneous metal fraction. The vector method developed in the current study showed the consistency with the potential methods. In Case 2, the model mimicked a scenario depicting post-evolutionary impact heating by assuming heterogeneous metal fractions. The results of Case 2 simultaneously represent the behavior of the solid mixture based on the density contrast and multiphase flow of the solid matrix and metallic pores. The checkerboard test (Case 3) used to evaluate the resolution of the numerical model as a function of the heat source size also indicated identical spatial resolutions for both methods. In all cases, two methods simulated identical physical behaviors, indicating that a three-dimensional model can be developed using the vector method. The 2D FEM vector method developed in this study was effectively utilized to simulate the advection scheme, showing the fast descent of metal phases and relatively slower silicate phases. We extended the 2D FEM vector method to calculate the velocity fields of silicate, Darcy, and iron metal in a 3D model with an impact heating case (similar to Case 1). The 3D results show that the velocity of fluid metal in 3D model is faster than that in 2D model, suggesting the difference in the resistance to viscous flow depending the dimension of model. Our 3D vector method, implemented in FEniCS, demonstrates the numerical prospect of the methods necessary to model the multiphase fluid dynamics of a 3D planetary evolution.

Sexual dimorphism in prevalence, severity and genetic susceptibility exists for most common diseases. However, most genetic and clinical outcome studies are designed in sex-combined framework considering sex as a covariate. Few sex-specific studies have analyzed males and females separately, which failed to identify gene-by-sex interaction. Here, we propose a novel unified biologically interpretable deep learning-based framework (named SPIN) for sexual dimorphism analysis. We demonstrate that SPIN significantly improved the C-index up to 23.6% in TCGA cancer datasets, and it was further validated using asthma datasets. In addition, SPIN identifies sex-specific and -shared risk loci that are often missed in previous sex-combined/-separate analysis. We also show that SPIN is interpretable for explaining how biological pathways contribute to sexual dimorphism and improve risk prediction in an individual level, which can result in the development of precision medicine tailored to a specific individual’s characteristics.

Silicon (Si) has an important role in forest ecology, but controls on Si availability in tropical forests remain poorly understood. For example, it remains unclear to what extent recycling from litterfall maintains Si availability in the soil, or whether Si is influenced by the dynamics of other essential nutrients. To address this, we quantified soil Si pools in two long-term experiments in lowland tropical forest in Panama: (i) a litter manipulation experiment involving 15 years of litter addition and removal, and (ii) a fertilizer experiment involving 20 years of nitrogen, phosphorus, and potassium addition. We quantified available Si extracted in 0.01 M CaCl2, reactive pedogenic Si extracted in acidic ammonium oxalate, and biogenic Si extracted in hot 1% Na2CO3. Fifteen years of litter manipulation reduced available Si by 17% where litter was removed and increased it by 53% where litter was added. Litter addition also increased reactive pedogenic Si by 43%, but there was no change with litter removal. Twenty years of nitrogen addition reduced available Si by 22% and pedogenic Si by 25%, but there were no significant responses to the addition of phosphorus or potassium. The decline in Si with nitrogen addition appears to be related to the mobilization and leaching of available Si during soil acidification. Biogenic Si did not respond to any treatment, including long-term litter addition involving an estimated annual return of 7.64 g Si m⁻² in leaf litterfall, suggesting that extraction with Na2CO3 is unsuitable for quantifying phytoliths in clay-rich tropical soils. Overall, these findings demonstrate the importance of litterfall in maintaining Si availability in tropical forests and highlight a rarely considered consequence of atmospheric nitrogen addition and associated soil acidification for the tropical Si cycle.

The growing interest in forward osmosis (FO) for water reclamation and desalination over the past two decades stems from its potential for lower energy consumption. Despite its promise, FO faces significant challenges, such as the lack of an appropriate draw solute, concentration polarization, membrane fouling, and reverse solute flux (RSF). Recent trends in research have focused on combining various technologies with FO to address these challenges. Notably, the integration of electrochemical technologies with FO offers new possibilities. This review covers FO combined with electrochemical cells (FO‐ECs), categorizing them based on their working principles and applications in improving FO. The review discusses different FO‐EC configurations, including (1) electrodialysis‐combined FO for RSF, (2) electro‐FO for water flux enhancement, and (3) electrochemical oxidation‐combined FO and FO with electro‐conductive membranes for self‐cleaning and fouling mitigation. Additionally, it covers (4) reusable electro‐responsive draw solutes, (5) electrochemical osmosis systems for metal removal and energy production, and (6) osmotic microbial fuel cells for energy recovery and other benefits. The review also assesses the practical applicability and potential for achieving carbon neutrality of the FO‐ECs. It concludes with a forward‐looking perspective, outlining future research directions to optimize and expand the use of electrochemical‐enhanced FO technologies.

The biogeographical range shift of insect pests is primarily governed by temperature. However, the range shift of seasonal long-distance migratory insects may be very different from that of sedentary insects. Nilaparvata lugens (BPH), a serious rice pest, can only overwinter in tropical-to-subtropical regions, and some populations migrate seasonally to temperate zones with the aid of low-level jet stream air currents. This study utilized the CLIMEX model to project the overwintering area under the climate change scenarios of RCP2.6 and RCP8.5, both in 2030s and 2080s. The overwintering boundary is predicted to expand poleward and new overwintering areas are predicted in the mid-latitude regions of central-to-eastern China and mid-to-southern Australia. With climate change, the habitable areas remained similar, but suitability decreased substantially, especially in the near-equatorial regions, owing to increasing heat stress. The range shift is similar between RCP2.6-2030s, RCP2.6-2080s, and RCP8.5-2030s, but extreme changes are projected under RCP8.5-2080s with marginal areas increasing from 27.2 to 38.8% and very favorable areas dropping from 27.5 to 3.6% compared to the current climate. These findings indicate that climate change will drive range shifts in BPH and alter regional risks differently. Therefore, international monitoring programs are needed to effectively manage these emerging challenges.

Aerial surveying with unmanned aerial vehicles (UAVs) has been popularly employed in river management and flood monitoring. One of the major processes in UAV aerial surveying for river applications is to demarcate the cross-section of a river. From the photo images of aerial surveying, a point cloud dataset can be abstracted with the structure from the motion technique. To accurately demarcate the cross-section from the cloud points, an appropriate delineation technique is required to reproduce the characteristics of natural and manmade channels, including abrupt changes, bumps and lined shapes. Therefore, a nonparametric estimation technique, called the K-nearest neighbor local linear regression (KLR) model, was tested in the current study to demarcate the cross-section of a river with a point cloud dataset from aerial surveying. The proposed technique was tested with synthetically simulated trapezoidal, U-shape and V-shape channels. In addition, the proposed KLR model was compared with the traditional polynomial regression model and another nonparametric technique, locally weighted scatterplot smoothing (LOWESS). The experimental study was performed with the river experiment center in Andong, South Korea. Furthermore, the KLR model was applied to two real case studies in the Migok-cheon stream on Hapcheon-gun and Pori-cheon stream on Yecheon-gun and compared to the other models. With the extensive applications to the feasible river channels, the results indicated that the proposed KLR model can be a suitable alternative for demarcating the cross-section of a river with point cloud data from UAV aerial surveying by reproducing the critical characteristics of natural and manmade channels, including abrupt changes and small bumps as well as different shapes. Finally, the limitation of the UAV-driven demarcation approach was also discussed due to the penetrability of RGB sensors to water.

Background: Although osteoarthritis (OA) development is epidemiologically multifactorial, a primary underlying mechanism is still under debate. Understanding the pathophysiology of OA remains challenging. Recently, experts have focused on autophagy as a contributor to OA development. Method: To better understand the pathogenesis of OA, we survey the literature on the role of autophagy and the molecular mechanisms of OA development. To identify relevant studies, we used controlled vocabulary and free text keywords to search the MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and SCOPUS database. Thirty-one studies were included for data extraction and systematic review. Among these studies, twenty-five studies investigated the effects of autophagy in aging and OA chondrocytes, six studies examined the effects of autophagy in normal human chondrocytes, and only one study investigated the effects of mechanical stress-induced autophagy on the development of OA in normal chondrocytes. Results: The studies suggest that autophagy activation prevents OA by exerting cell-protective effects in normal human chondrocytes. However, in aging and osteoarthritis (OA) chondrocytes, the role of autophagy is intricate, as certain studies indicate that stimulating autophagy in these cells can have a cytotoxic effect, while others propose that it may have a protective (cytoprotective) effect against damage or degeneration. Conclusions: Mechanical stress-induced autophagy is also thought to be involved in the development of OA, but further research is required to identify the precise mechanism. Thus, autophagy contributions should be interpreted with caution in aging and the types of OA cartilage.

This study examines subaqueous dunes located on the southern periphery of the flat top of Dokdo Seamount at water depths from 120 to 170 m where the present ocean currents are incapable of generating such large bedforms. To determine their origin, we conducted a comprehensive analysis of the geomorphic characteristics using high-resolution multi-beam bathymetry and the grain-size characteristics of seafloor sediments. The analysis of the dune spacing in relation to height, as well as their migration and growth pattern, indicates that the Dokdo subaqueous dunes (DSDs) originally formed as aeolian dunes. These were shaped by northerly winter winds that carried sands from the wave erosion surfaces on the northern part of the flat top. The DSDs are believed to have transitioned to their current submerged state without experiencing significant erosion or reactivation. Considering the variations in the Plio-Pleistocene global mean sea level, we estimate the possible subsidence rate of the flat top to be approximately 130 m/myrs, aligning with the conditions required for the formation of DSDs. This study highlights how relict features such as submerged aeolian dunes on seamount summits can be utilized to precisely estimate the subsidence rate of oceanic volcanoes.

The current research was the first to prove the existence of fluctuations in the metabolite constituents and antioxidant properties in different organs (leaves, stems, and roots) of the mountain-cultivated ginseng (MCG) plant during a two-month maturation period. Four metabolites, including fatty acids, amino acids, ginsenosides, and phenolic phytochemicals, exhibited considerable differences in organs and maturation times with the following order: leaves > stems > roots. The predominant metabolite contents were found in leaves, with fatty acid (1057.9 mg/100 g) on 31 May, amino acid (1989.2 mg/100 g) on 13 July, ginsenosides (88.7 mg/g) on 31 May, and phenolic phytochemical (638.3 μg/g) on 31 May. Interestingly, ginsenoside content in leaves were highest, with 84.8 → 88.7 → 82.2 → 78.3 mg/g. Specifically, ginsenosides Re, Rd, and F2 showed abundant content ranging from 19.1 to 16.9 mg/g, 8.5 to 14.8 mg/g, and 9.5 to 13.1 mg/g, respectively. Phenolic phytochemicals exhibited remarkable differences in organs compared to maturation periods, with the highest total phenolic content and total flavonoid content recorded at 9.48 GAE and 1.30 RE mg/g in leaves on 31 May. The antioxidant capacities on radical, FRAP, and DNA protection differed significantly, with leaves on 31 May exhibiting the highest values: 88.4% (DPPH), 89.5% (ABTS), 0.84 OD593 nm (FRAP) at 500 μg/mL, and 100% DNA protection at 50 μg/mL. Furthermore, principal cluster analysis revealed metabolite variability as follows: ginsenoside (83.3%) > amino acid (71.8%) > phenolic phytochemical (61.1%) > fatty acid (58.8%). A clustering heatmap highlighted significant changes in metabolite components under the maturation times for each organ. Our findings suggest that MCG leaves on 31 May may be a potential source for developing nutraceuticals, offering highly beneficial components and strong antioxidants.

Ultraviolet B (UVB) irradiation causes photoaging, such as wrinkles, roughness and dryness of the skin, and it activates the production of reactive oxygen species (ROS) and inflammatory cytokines. In this study, the anti-photoaging activity of SEP-E (steam-exploded pine extract) was evaluated in HaCaT keratinocytes damaged by UVB irradiation. SEP-E treatment showed cytoprotective effects in HaCaT keratinocytes irradiated with UVB (40 mJ/cm2). SEP-E treatment reduced ROS overproduction and promoted the expression of antioxidant enzymes, such as catalase, superoxide dismutase 1, and superoxide dismutase 2. Additionally, SEP-E treatment suppressed the expression of inflammatory cytokines, including interleukin 6, interleukin 8, and monocyte chemoattractant protein-1. Consequently, SEP-E shows potential as a natural material for photoaging treatment.

Myxomatous mitral valve disease (MMVD) is the most common cardiovascular disorder in dogs with a high prevalence, accounting for approximately 75% of all canine heart disease cases. MMVD is a complex disease and shows variable progression from mild valve leakage to severe regurgitation, potentially leading to heart failure. However, the molecular mechanisms and age-related changes that govern disease progression, especially at the early stage (B1) before the development of discernable clinical signs, remain poorly understood. In this prospective study, we aimed to compare gene expression differences between blood samples of aged beagle dogs with stage B1 MMVD and those of healthy controls using RNA sequencing. Clinical evaluation was also conducted, which revealed minimal differences in radiographic and echocardiographic measurements despite distinct biomarker variations between the two groups. Comparative transcriptomics revealed differentially expressed genes associated with extracellular matrix remodeling, prostaglandin metabolism, immune modulation, and interferon-related pathways, which bear functional relevance for MMVD. In particular, the top 10 over- and under-expressed genes represent promising candidates for influencing pathogenic changes in MMVD stage B1. Our research findings, which include identified variations in clinical markers and gene expression, enhance our understanding of MMVD. Furthermore, they underscore the need for further research into early diagnosis and treatment strategies, as, to the best of our knowledge, no prior studies have explored the precise molecular mechanisms of stage B1 in MMVD through total RNA sequencing.

Ischemic stroke causes a lack of oxygen and glucose supply to brain, eventually leads to severe neurological disorders. Retinoic acid is a major metabolic product of vitamin A and has various biological effects. The PI3K-Akt signaling pathway is an important survival pathway in brain. Phosphorylated Akt is important in regulating survival and apoptosis. We examined whether retinoic acid has neuroprotective effects in stroke model by regulating Akt and its downstream protein, Bad. Moreover, we investigated the relationship between retinoic acid and Bcl-2 family protein interactions. Animals were intraperitoneally administered vehicle or retinoic acid (5 mg/kg) for four days before surgery and ischemic stroke was induced by middle cerebral artery occlusion (MCAO) surgery. Neurobehavioral tests were performed 24 h after MCAO and cerebral cortical tissues were collected. Cresyl violet staining and TUNEL histochemistry were performed, Western blot and immunoprecipitation analysis were performed to elucidate the expression of various proteins. Retinoic acid reduced neurological deficits and histopathological changes, decreased the number of TUNEL-positive cells, and alleviated reduction of phospho-PDK1, phospho-Akt, and phospho-Bad expression caused by MCAO damage. Immunoprecipitation analysis showed that MCAO damage reduced the interaction between phospho-Bad and 14-3-3, which was attenuated by retinoic acid. Furthermore, retinoic acid mitigated the increase in Bcl-2/Bad and Bcl-xL/Bad binding levels and the reduction in Bcl-2/Bax and Bcl-xL/Bax binding levels caused by MCAO damage. Retinoic acid alleviated MCAO-induced increase of caspase-3 and cleaved caspase-3 expression. We demonstrate that retinoic acid prevented apoptosis against cerebral ischemia through phosphorylation of Akt and Bad, maintenance of phospho-Bad and 14-3-3 binding, and regulation of Bcl-2 family protein interactions.