# Pusan National University

• Busan, Busan, South Korea
Recent publications
The gut microbiota is essential for maintenance and repair of the intestinal epithelial barrier. As shifts in both intestinal epithelial barrier function and microbiota composition are found in inflammatory bowel disease patients, it is critical to understand the role of distinct bacteria in regulating barrier repair. We identified a mouse commensal E. coli isolate, GDAR2-2, that protects mice from Citrobacter rodentium infection and dextran sulfate sodium-induced colitis. Colonization with GDAR2-2 in mice resulted in expansion of CX3CR1⁺ mononuclear phagocytes, including CX3CR1⁺ macrophages/dendritic cells and monocytes, along with IL-22-secreting type 3 innate lymphoid cells and improved epithelial barrier function. In vitro co-culture of macrophages with GDAR2-2 resulted in IL-1β production. In vivo, protection after GDAR2-2 colonization was lost after depletion of CX3CR1⁺ MNPs, or blockade of IL-1β or IL-22. We further identified human commensal E. coli isolates that similarly protect mice from C. rodentium infection through CX3CR1⁺ MNP and IL-1β production. Together, these findings demonstrate an unexpected role for commensal bacteria in promoting IL-1β secretion to support intestinal barrier repair.
Alternative splicing (AS) contributes to diversifying and regulating cellular responses to environmental conditions and developmental cues by differentially producing multiple mRNA and protein isoforms from a single gene. Previous studies on AS in pathogenic fungi focused on profiling AS isoforms under a limited number of conditions. We analysed AS profiles in the rice blast fungus Magnaporthe oryzae, a global threat to rice production, using high-quality transcriptome data representing its vegetative growth (mycelia) and multiple host infection stages. We identified 4,270 AS isoforms derived from 2,413 genes, including 499 genes presumably regulated by infection-specific AS. AS appears to increase during infection, with 32.7% of the AS isoforms being produced during infection but absent in mycelia. Analysis of the isoforms observed at each infection stage showed that 636 AS isoforms were more abundant than corresponding annotated mRNAs, especially after initial hyphal penetration into host cell. Many such dominant isoforms were predicted to encode regulatory proteins such as transcription factors and phospho-transferases. We also identified the genes encoding distinct proteins via AS and confirmed the translation of some isoforms via a proteomic analysis, suggesting potential AS-mediated neo-functionalization of some genes during infection. Comprehensive profiling of the pattern of genome-wide AS during multiple stages of rice-M. oryzae interaction established a foundational resource that will help investigate the role and regulation of AS during rice infection.
Background Non-vitamin K antagonist oral anticoagulants (NOACs) are preferred over vitamin K antagonists (VKAs) as oral anticoagulant (OAC) therapy in patients with nonvalvular atrial fibrillation (NVAF). This study aimed to estimate the current status and risk factors of OAC underutilization in the NOAC era. Method A cross-sectional study using nationwide claims data was conducted. Elderly patients with NVAF at an increased risk of stroke were selected as candidates for OAC therapy before the index date (July 1, 2018). The status of anticoagulant utilization on the index date and factors influencing the use of anticoagulants was investigated in these patients. Results Of the 11,056 patients with NVAF who were eligible for OAC therapy, 7238 (65.5%) were receiving OAC on the index date, and 6302 (87.1%) were receiving NOACs. Patients aged ≥ 75 years had higher anticoagulant utilization than those aged 65–69 years. Among comorbid diseases, while hypertension was the most influential positive factor (odds ratio [OR] = 1.644; confidence interval [CI] = 1.445–1.869) in OAC utilization, severe renal disease was the most influential negative factor (OR = 0.289; CI = 0.200–0.416). Aspirin use had a significantly low OR (OR = 0.097; CI = 0.085–0.110) of anticoagulant use. OAC use was approximately 1.5 times higher in patients with persistent or permanent AF than in those with paroxysmal AF. Conclusion Approximately one-third of patients who are recommended anticoagulation therapy do not take OACs, even though the use of NOACs has become more common. It should be widely recognized that aspirin cannot be an alternative to OACs, and anticoagulant therapy should be actively implemented.
The intra-seasonal variation in precipitation isotopes shows a characteristic declining trend over northeast India. As of now, no mechanism offers a consistent explanation of this trend. We have performed the isotopic analysis of precipitation (rain) and estimated net ecosystem exchange and latent heat fluxes using an eddy-covariance system in northeast India. Additionally, we have used a diagnostic model to determine the recycled rainfall in this region. We find a strong link between the enhanced ecosystem productivity and isotopic enrichment in rainwater during the premonsoon season. Subsequently, on the advent of monsoon, the Bay of Bengal generated moisture enters this region and depletes the isotopic values. Additionally, the regional-scale convective activities produce periodic lows in the precipitation isotopes. Contrary to the general understanding, our study shows that the internal factors, such as the local land-atmosphere interactions, rather than the external influences, play a significant role in governing the precipitation isotopes in northeast India.
The liner of a CNG pressure vessel is manufactured by a DDI (deep drawing and ironing) process for the cylinder part, which is a continuous process that includes a drawing process to reduce the diameter of the billet and a subsequent ironing process to reduce the thickness of the billet. A tractrix die used in the 1 st deep drawing allows the blank to flow smoothly by decreasing the punch load and radial tensile stress occurring in the workpiece. It also increases the draw ratio compared to conventional dies, but it causes forming defects. In this study, a shape coefficient ( S c ) is proposed for the tractrix die using the blank diameter ( D 0 ), inflow diameter of the workpiece ( d i ), and inflow angle of the workpiece ( $$\theta$$ θ ) for design of the tractrix die. The effects of the thickness and inflow angle of the workpiece on wrinkling and folding were investigated through FEA. Also, a discriminant is proposed for the relative radial stress ( $$\tilde{\sigma }$$ σ ~ ) generated during the deep drawing process using the tractirx die and used to predict fracture. Based on the results, the blank thickness, the draw ratio, and the inflow of the workpiece angle in the 1 st deep drawing process are suggested, and the number of operations in the DDI process was reduced from 6 to 4. This improves the productivity and reduces the manufacturing cost.
The recent discovery of a two-dimensional van der Waals magnet has paved the way for an enhanced understanding of two-dimensional magnetic systems. The development of appropriate heterostructures in this emerging class of materials is required as the next step towards applications. Here, we report on the electrical transport in monolayer graphene coupled with the two-dimensional ferromagnet Cr 2 Ge 2 Te 6 (CGT). Graphene that forms an interface with CGT is electron-doped owing to charge transfer. The temperature-dependent resistance of graphene/CGT undergoes a nontrivial sudden change near the Curie temperature ( T c ) of CGT. Apart from this, the behavior of various transport parameters also differs before and after T c . Moreover, the contribution of the magnetization of CGT to the enhanced magnetic flux density leads to the critical evolution of the quantum Hall state. These results imply that graphene in the graphene/CGT hybrid structure can be utilized to electrically monitor the magnetic phase transition of the adjacent CGT layer.
Background The implants of pure titanium (Ti) and its alloys can lead to implant failure because of their poor interaction with bone-associated cells during bone regeneration. Surface modification over implants has achieved successful implants for enhanced osseointegration. Herein, we report a robust strategy to implement bioactive surface modification for implant interface enabled by the combinatorial system of reduced graphene oxide (rGO)-coated sandblasted, large-grit, and acid-etched (SLA) Ti to impart benefits to the implant. Methods We prepared SLA Ti (ST) implants with different surface modifications [i.e., rGO and recombinant human bone morphogenetic protein-2 (rhBMP-2)] and investigated their dental tissue regenerating ability in animal models. We performed comparative studies in surface property, in vitro cellular behaviors, and in vivo osseointegration activity among different groups, including ST (control), rhBMP-2-immobilized ST (BI-ST), rhBMP-2-treated ST (BT-ST), and rGO-coated ST (R-ST). Results Spectroscopic, diffractometric, and microscopic analyses confirmed that rGO was coated well around the surfaces of Ti discs (for cell study) and implant fixtures (for animal study). Furthermore, in vitro and in vivo studies revealed that the R-ST group showed significantly better effects in cell attachment and proliferation, alkaline phosphatase activity, matrix mineralization, expression of osteogenesis-related genes and protein, and osseointegration than the control (ST), BI-ST, and BT-ST groups. Conclusion Hence, we suggest that the rGO-coated Ti can be a promising candidate for the application to dental or even orthopedic implants due to its ability to accelerate the healing rate with the high potential of osseointegration.
Background The diagnostic yield of whole-exome sequencing (WES) varies from 30%–50% among patients with mild to severe neurodevelopmental delay (NDD)/intellectual disability (ID). Routine retrospective reanalysis of undiagnosed patients has increased the total diagnostic yield by 10–15%. Here, we performed proband-only WES of 1065 patients with NDD/ID and applied a prospective, daily reanalysis automated pipeline to patients without clinically significant variants to facilitate diagnoses. Methods The study included 1065 consecutive patients from 1056 nonconsanguineous unrelated families from 10 multimedical centers in South Korea between April 2018 and August 2021. WES data were analyzed daily using automatically updated databases with variant classification and symptom similarity scoring systems. Results At the initial analysis, 402 patients from 1056 unrelated families (38.0%, 402/1,056 families) had a positive genetic diagnosis. Daily prospective, automated reanalysis resulted in the identification of 34 additional diagnostic variants in 31 patients (3%), which increased our molecular diagnostic yield to 41% (433/1056 families). Among these 31 patients, 26 were diagnosed with 23 different diseases that were newly discovered after 2019. The time interval between the first analysis and the molecular diagnosis by reanalysis was 1.2 ± 0.9 years, which was shorter in the patients enrolled during the latter part of the study period. Conclusion Daily updated databases and reanalysis systems enhance the diagnostic performance in patients with NDD/ID, contributing to the rapid diagnosis of undiagnosed patients by applying the latest molecular genetic information.
The programmed cell death ligand 1 (PD-L1) and its receptor programmed cell death 1 (PD-1) deliver inhibitory signals to regulate immunological tolerance during immune-mediated diseases. However, the role of PD-1 signaling and its blockade effect on human dental pulp stem cells (hDPSCs) differentiation into the osteo-/odontogenic lineage remain unknown. We show here that PD-L1 expression, but not PD-1, is downregulated during osteo-/odontogenic differentiation of hDPSCs. Importantly, PD-L1/PD-1 signaling has been shown to negatively regulate the osteo-/odontogenic differentiation of hDPSCs. Mechanistically, depletion of either PD-L1 or PD-1 expression increased ERK and AKT phosphorylation levels through the upregulation of Ras enzyme activity, which plays a pivotal role during hDPSCs osteo-/odontogenic differentiation. Treatment with nivolumab (a human anti-PD-1 monoclonal antibody), which targets PD-1 to prevent PD-L1 binding, successfully enhanced osteo-/odontogenic differentiation of hDPSCs through enhanced Ras activity-mediated phosphorylation of ERK and AKT. Our findings underscore that downregulation of PD-L1 expression accompanies during osteo-/odontogenic differentiation, and hDPSCs-intrinsic PD-1 signaling inhibits osteo-/odontogenic differentiation. These findings provide a significant basis that PD-1 blockade could be effective immunotherapeutic strategies in hDPSCs-mediated dental pulp regeneration.
Successful cultivation of rice ( Oryza sativa L.) in many Asian countries requires submergence stress tolerance at the germination and early establishment stages. Two quantitative trait loci, Sub1 (conferring submergence tolerance) and AG1 (conferring anaerobic germination), were recently pyramided into a single genetic background, without compromising any desirable agronomic traits, leading to the development of Ciherang-Sub1 + AG1 (CSA). However, little research has been conducted to enhance plant tolerance to abiotic stress (submergence) and biotic stress (rice blast), which occur in a damp climate following flooding. The BC 2 F 5 breeding line was phenotypically characterized using the AvrPi9 isolate. The biotic and abiotic stress tolerance of selected lines was tested under submergence stress and anaerobic germination conditions, and lines tolerant to each stress condition were identified through phenotypic and gene expression analyses. The Ciherang-Sub1 + AG1 + Pi9 (CSA-Pi9) line showed similar agronomic performance to its recurrent parent, CSA, but had significantly reduced chalkiness in field trials conducted in temperate regions. Unexpectedly, the CSA-Pi9 line also showed salinity tolerance. Thus, the breeding line newly developed in this study, CSA-Pi9, functioned under stress conditions, in which Sub1 , AG1 , and Pi9 play a role and had superior grain quality traits compared to its recurrent parent in temperate regions. We speculate that CSA-Pi9 will enable the establishment of climate-resilient rice cropping systems, particularly in East Asia.
An earthquake swarm occurred in Haulien, Taiwan, from April 7 to August 31, 2021. The epicenters are in the range from 23°47′ N to 24°04′ N and from 121°25′ E to 121°42′ E. C q ( r ) and C q ( t ) are the generalized correlation integral of r and t , respectively. From the events with local magnitudes ≥ 3 and focal depths ≤ 25 km, C q ( r ) is calculated for the epicentral and hypocentral distribution (using the distance between two events, r ) and C q ( t ) for the time sequence (using the inter-event time between two events, t ). The multifractal dimension D q (q = 2, 3, …, 15) is the slope of the linear portion of the log–log plots of C q ( r ) versus r as well as C q ( t ) versus t . For the epicentral distribution, the linear pattern is in the range 0.5 ≤ log( r ) ≤ 1.3. The measured values of D q are all smaller than 2 that is the spatial dimension and monotonically decreases with increasing q . This indicates that the epicentral distribution of the swarm is multifractal. For the hypocentral distribution, a lack of a wide enough linear pattern on the log–log plot makes the hypocentral distribution be not multifractal. For the time sequence, the log–log plot of C q ( t ) versus t shows a linear pattern in the range 0.5 ≤ log( t ) ≤ 1.0. The values of D q are all smaller than 1 that is the time dimension and monotonically decreases with increasing q , thus suggesting multifractality of the time sequence when t is shorter than the maximum inter-event time.
Objective The description of controls is important in acupuncture clinical trials to interpret its effectiveness without fallacy. This paper aims to evaluate the reporting quality of acupuncture studies on the characteristics of sham needles. Study design and setting Using a checklist developed from previously published reporting guidelines, the distribution of reported items and changes of reporting rates over time were investigated. Two-way ANOVA and linear regression were conducted. Results Original articles of RCTs of any design involving sham needles as controls were eligible for assessment. 117 trials from three 2-year time periods between 2009 and 2018 were included. Seven items out of 25 were reported in more than 50% of the studies. While significant differences of reporting scores among categories were observed, there were no significant differences among time periods; no significant improvement was observed over time. Conclusions Low reporting qualities of sham needles used in acupuncture studies may influence how researchers understand the effectiveness of acupuncture. This study evaluated previous publications from 2009 to 2018 and found that reporting qualities on sham needles did not improve over time. Further studies are required to validate the items used in this study to endorse better reporting of controls in acupuncture trials.
Background Hypoalbuminemia at the initiation of continuous renal replacement therapy (CRRT) is a risk factor for poor patient outcomes. However, it is unknown whether the patterns of changes in serum albumin levels during CRRT can be used to predict patient outcomes. Methods This retrospective study analyzed data that had been consecutively collected from January 2016 to December 2020 at the Third Affiliated Hospital. We included patients with acute kidney injury who received CRRT for ≥ 72 h. We divided the patients into four groups based on their serum albumin levels (albumin ≥ 3.0 g/dL or < 3.0 g/dL) at the initiation and termination of CRRT. Results The 793 patients in this study were categorized into the following albumin groups: persistently low, 299 patients (37.7%); increasing, 85 patients (10.4%); decreasing, 195 patients (24.6%); and persistently high, 214 patients (27.1%). In-hospital mortality rates were highest in the persistently low and decreasing groups, followed by the increasing and persistently high groups. The hazard ratio for in-hospital mortality was 0.481 (0.340–0.680) in the increasing group compared to the persistently low group; it was 1.911 (1.394–2.620) in the decreasing group compared to the persistently high group. The length of ICU stay was 3.55 days longer in the persistently low group than in the persistently high group. Conclusions Serum albumin levels changed during CRRT, and monitoring of patterns of change in serum albumin levels is useful for predicting in-hospital mortality and the length of ICU stay.
The standard Z-type schlieren visualization technique was used to experimentally investigate the effects of inlet boundary conditions (temperature and pressure) and nozzle geometry (convergent and convergent-divergent nozzles (C-D)) on a supersonic flow structure. The focus was on the Mach disk's length (Lm) and width (Wm). The inlet temperature (Tin) was 123 to 288 K, and the nozzle pressure ratio (NPR=Pin/Patm) was 3 to 20. When varying the NPR, over and under-expanded flow conditions were observed in the studied nozzle configurations. The results illustrate that when increasing NPR at Tin = 288 K, Lm increases for both over and under-expanded flow conditions. However, when increasing NPR in over-expanded conditions, Wm increases to reach the saturation point and then decreases for a C-D nozzle with a larger exit diameter, while it becomes constant for a small exit diameter. In contrast, Wm increased when increasing NPR for all nozzles in the under-expanded regime. At 123 K < Tin < 173 K, the shock cells were shrunken for C-D nozzles at NPR=5, and subsequently, Lm decreased. Nevertheless, Wm increased until Tin = 153 K and then decreased until Tin = 123 K, which disturbed the Mach disks and shock cells that governed the decrease in Wm.
According to the mass law, a dense and thick soundproofing material is generally used to block low-frequency sounds. However, lightweight thin soundproofing materials in the form of metamaterials can also be implemented with high sound transmission loss. In this study, we present a soundproofing comprising a thin membrane coupled with an ultralight membrane-type acoustic metamaterial (MAM). Owing to the vibration in the membrane, the structure-borne acoustic radiation of the soundproofing can be easily tuned, making broadband sound insulation possible. The anti-resonance generated by the membrane and thin plate surface minimizes the response of the radiating surface to the acoustic load. Thus, the dynamic effective density and acoustic impedance become extremely high, whereas the normal displacement of the radiating surface is almost zero. We numerically and experimentally demonstrated an open-field test for a plate-type and an enclosure-type of soundproofing MAM. In addition, the vibration displacement of the MAM enclosure exterior wall is measured using laser Doppler vibrometer. The results show that the soundproofing MAM exhibits excellent sound-blocking characteristics at multiple anti-resonance frequencies compared to homogeneous materials of the same weight. We expect that its simple construction can be used in noise-insulation applications in acoustic enclosures, automobile insulation, walls, and engine rooms.
Herein, catalytic effects of Zn and Mo-loaded HZSM-5 on pyrolysis of food waste (FW) under methane (CH4) and a hydrogen (H2)-rich gas stream derived from catalytic CH4 decomposition (CH4-D) over a Ni–La2O3–CeO2/Al2O3 were explored as a method to produce high-value biochemicals such as benzene, toluene, ethylbenzene, and xylenes (BTEX). The CH4-D pyrolysis medium led to a higher BTEX yield than a typical pyrolysis medium (e.g., nitrogen) and CH4 medium because it provided a H2-rich environment during the FW pyrolysis (e.g., H2/CO2 ratio = 1.01), thereby facilitating hydropyrolysis and hydrodeoxygenation of pyrolytic vapors evolved from FW. The H2-rich environment also helped to reduce coke deposition on the catalyst. Under CH4-D environment, a bimetallic Zn–Mo catalyst supported on HZSM-5 (Zn–Mo/HZSM-5) maximized the BTEX yield (19.93 wt.%) compared to HZSM-5 and monometallic Zn and Mo catalysts. This is most likely because the bimetallic catalyst possessed the highest number of total acid sites among all the tested catalysts. The high acidity and H2-rich media (CH4-D) synergistically promoted aromatization, hydrodeoxygenation, and hydrodealkylation reactions, which enhanced the BTEX yield. The Zn–Mo/HZSM-5-catalyzed FW pyrolysis under CH4-D environment would be an eco-friendly and sustainable strategy to transform unmanageable organic waste (e.g., FW) into high-value biochemicals such as bioaromatics.
As an important part of the Design for X tools, Design for Quality (DFQ) is used to reduce cost and improve quality of products while maintaining reliability in preliminary design phase. As a powerful tool to reduce and eliminate possible failures, failure mode and effects analysis (FMEA) is broadly applied in detail design phase. However, scholars have criticized the traditional FMEA model for several shortages. In the past decades, nearly all the FMEA methods have been presented to heighten the rationality of ranking results by considering the risk factors (severity (S), occurrence (O) and detection (D)) simultaneously. The simultaneous analysis of risk factors (RFs) may result in the ignorance of impact on failure modes from extreme RFs. In fact, different combinations of RFs may obtain more comprehensive risk information about failure modes. Thus, a novel FMEA classification method is proposed by combining risk factors in pairs (i.e., S&O, S&D and O&D) to conduct risk assessment which can avoid interaction effect caused by simultaneous analysis of risk factors. Specifically, the fuzzy adaptive resonance theory is used to conduct failure modes classification based on the assessment results of S&O, S&D and O&D obtained by the grey relational analysis. Finally, a real case study, i.e., the final assembly process of spark plugs, from an automotive manufacturer in China is adopted to clarify the advantages of the proposed method.
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• School of Computer Science and Engineering
• Department of Polymer Science and Engineering
• Department of Bioenvironmental Energy
• College of Medicine
• Department of Biological Sciences
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