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Objectives: Non-typhoid Salmonella infection is a major agent of food-borne outbreaks as well as individual cases worldwide. However, few studies on drug-resistant Salmonella strains, especially those recovered from young children, are available. Therefore, we determined the prevalence and characteristics of cephalosporin-resistant Salmonella isolates in the south-west region of Korea over a five-year period. Methods: Non-duplicate Salmonella clinical isolates were recovered from diarrhoeagenic patient specimens at 12 hospitals in Gwangju, Korea between January 2014 and December 2018. Antimicrobial susceptibility testing and molecular features of cephalosporin-resistant isolates were determined. Results: A total of 652 Salmonella isolates were collected and 48 cefotaxime-resistant Salmonella isolates (7.4%), that belonged to nine Salmonella serovars, were identified. These were S. Enteritidis, S. Typhimurium, S. I 4,[5],12:i:-, S. Virchow, S. Agona, S. Bareilly, S. Infantis, S. Newport, and S. Schleissheim. The prevalence rate increased from 5.3% in 2014 to 10.3% in 2018. S. Virchow (44.4%) showed significantly high resistant rate compared to the other serovars. PGFE genotyping revealed high genetic homogeneities among each Salmonella serovars, suggesting clonal dissemination of cephalosporin-resistant strains. Conclusions: Progressive increases in carriage rates and the possibility of community outbreaks by cephalosporin-resistant Salmonella in young children may pose tangible public health threats.

Traditionally, medicine has held that some human body sites are sterile and that the introduction of microbes to these sites results in infections. This paradigm shifted significantly with the discovery of the human microbiome and acceptance of these commensal microbes living across the body. However, the central nervous system (CNS) is still believed by many to be sterile in healthy people. Using culture-independent methods, we examined the virome of cerebrospinal fluid (CSF) from a cohort of mostly healthy human subjects. We identified a community of DNA viruses, most of which were identified as bacteriophages. Compared to other human specimen types, CSF viromes were not ecologically distinct. There was a high alpha diversity cluster that included feces, saliva, and urine, and a low alpha diversity cluster that included CSF, body fluids, plasma, and breast milk. The high diversity cluster included specimens known to have many bacteria, while other specimens traditionally assumed to be sterile formed the low diversity cluster. There was an abundance of viruses shared among CSF, breast milk, plasma, and body fluids, while each generally shared less with urine, feces, and saliva. These shared viruses ranged across different virus families, indicating that similarities between these viromes represent more than just a single shared virus family. By identifying a virome in the CSF of mostly healthy individuals, it is now less likely that any human body site is devoid of microbes, which further highlights the need to decipher the role that viral communities may play in human health.

The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH)-smoothened (Smo) signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.

Background: Post-ovulatory aging (POA) of oocytes is related to a decrease in the quality and quantity of oocytes caused by aging. Previous studies on the characteristics of POA have investigated injury to early embryonic developmental ability, but no information is available on its effects on mitochondrial fission and mitophagy-related responses. In this study, we aimed to elucidate the molecular mechanisms underlying mitochondrial fission and mitophagy in in vitro maturation (IVM) oocytes and a POA model based on RNA sequencing analysis. Methods: The POA model was obtained through an additional 24 h culture following the IVM of matured oocytes. NMN treatment was administered at a concentration of 25 μM during the oocyte culture process. We conducted MitoTracker staining and Western blot experiments to confirm changes in mitochondrial function between the IVM and POA groups. Additionally, comparative transcriptome analysis was performed to identify differentially expressed genes and associated changes in mitochondrial dynamics between porcine IVM and POA model oocytes. Results: In total, 32 common genes of apoptosis and 42 mitochondrial fission and function uniquely expressed genes were detected (≥ 1.5-fold change) in POA and porcine metaphase II oocytes, respectively. Functional analyses of mitochondrial fission, oxidative stress, mitophagy, autophagy, and cellular apoptosis were observed as the major changes in regulated biological processes for oocyte quality and maturation ability compared with the POA model. Additionally, we revealed that the activation of NAD+ by nicotinamide mononucleotide not only partly improved oocyte quality but also mitochondrial fission and mitophagy activation in the POA porcine model. Conclusions: In summary, our data indicate that mitochondrial fission and function play roles in controlling oxidative stress, mitophagy, and apoptosis during maturation in POA porcine oocytes. Additionally, we found that NAD+ biosynthesis is an important pathway that mediates the effects of DRP1-derived mitochondrial morphology, dynamic balance, and mitophagy in the POA model.

ObjectivesWhile other cytokines are known to be associated with otitis media with effusion (OME), the involvement of heat shock protein 70 (HSP70) in middle ear effusion (MEE) is unknown. This study was undertaken to investigate the possibility of there being a HSP70 expression in human MEE and to determine its potential role as a cytokine in OME.MethodsThe levels of HSP70, tumor necrosis factor-alpha and interleukin-1beta were measured by enzyme-linked immunosorbent assay in the effusion of different groups of OME patient following collection of the MEE using our new collection system. The clinical characteristics of the OME patients and the MEE status were analyzed.ResultsHSP70 was expressed in all the types of MEE. The mucous and seromucous effusions showed higher HSP70 levels than that of the serous effusion. The HSP70 level was correlated with the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the effusions. The positive correlations between HSP70, TNF-α and IL-1β were statistically significant (P

Primary cilia are conserved cellular organelles that regulate diverse signaling pathways. Autophagy is a complex process of cellular degradation and recycling of cytoplasmic proteins and organelles, and plays an important role in cellular homeostasis. Despite its potential importance, the role of autophagy in ciliogenesis is largely unknown. In this study, we identified sertraline as a regulator of autophagy and ciliogenesis. Sertraline, a known antidepressant, induced the growth of cilia and blocked the disassembly of cilia in htRPE cells. Following treatment of sertraline, there was an increase in the number of cells with autophagic puncta and LC3 protein conversion. In addition, both a decrease of ATG5 expression and the treatment of an autophagy inhibitor resulted in the suppression of the sertraline-induced activation of autophagy in htRPE cells. Interestingly, we found that genetic and chemical inhibition of autophagy attenuated the growth of primary cilia in htRPE cells. Taken together, our results suggest that the inhibition of autophagy suppresses sertraline-induced ciliogenesis.

Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) secrete various beneficial molecules, which have anti-apoptotic activity and cell proliferation. However, the effect of hUCB-MSCs in melanogenesis is largely unclear. In this study, we show that conditioned media (CM) derived from hUCB-MSCs inhibit melanogenesis by regulating microphthalmia-associated transcription factor (MITF) expression via the ERK signalling pathway. Treatment of hUCB-MSC-CM strongly inhibited the alpha-melanocyte stimulating hormone-induced hyperpigmentation in melanoma cells as well as melanocytes. Treatment of hUCB-MSC-CM induced ERK1/2 activation in melanocytes. In addition, inhibition of ERK1/2 suppressed the anti-pigmentation activity of the hUCB-MSC-CM in melanocytes and in vitro artificial skin models. We also found that the expression of MITF was appreciably diminished while expression of phosphorylated MITF, which leads to its proteasomal degradation, was increased in cells treated with hUCB-MSC-CM. These results suggested that hUCB-MSC-CM significantly suppresses melanin synthesis via MITF degradation by the ERK pathway activation.

To date, several regulatory proteins involved in mitochondrial dynamics have been identified. However, the precise mechanism coordinating these complex processes remains unclear. Mitochondrial chaperones regulate mitochondrial function and structure. Chaperonin 10 (Cpn10) interacts with heat shock protein 60 (HSP60) and functions as a co-chaperone. In this study, we found that down-regulation of Cpn10 highly promoted mitochondrial fragmentation in SK-N-MC and SH-SY5Y neuroblastoma cells. Both genetic and chemical inhibition of Drp1 suppressed the mitochondrial fragmentation induced by Cpn10 reduction. Reactive oxygen species (ROS) generation in 3-NP-treated cells was markedly enhanced by Cpn10 knock down. Depletion of Cpn10 synergistically increased cell death in response to 3-NP treatment. Furthermore, inhibition of Drp1 recovered Cpn10-mediated mitochondrial dysfunction in 3-NP-treated cells. Moreover, an ROS scavenger suppressed cell death mediated by Cpn10 knockdown in 3-NP-treated cells. Taken together, these results showed that down-regulation of Cpn10 increased mitochondrial fragmentation and potentiated 3-NP-mediated mitochondrial dysfunction in neuroblastoma cells.

Building energy conservation measure (ECM) of insulation materials suitable for the domestic situation in the construction sector (passive) is established. The ECMs of insulation materials were classified into walls, roofs, and floors. Also, economic evaluation databases, which are composed of material costs, labor costs, and expenses for constructed alternatives, were built. After setting the target building and deriving the ECM list of insulation materials for the target building, the energy use evaluation and economic evaluation were performed for each constructed alternative. Based on this, the optimal building energy conservation measure of the target building was derived by applying the decision-support process.

ECO2 (building energy efficiency rating program) and passive energy conservation measures (ECMs) were established as a basic study for targeted methodologies and decision support systems development in Korea to meet national regulations. The primary energy consumption and economic evaluation of nonresidential buildings was performed. Passive ECMs were classified as planning and performance elements. The planning elements are the window-to-wall ratio (WWR) and horizontal shading angle. The performance elements are the thermal transmittance (U-value) of the walls, roof, and floor and the U-value and solar heat gain coefficient (SHGC) of windows. This study focused on the window-to-wall ratio and the U-value and solar heat gain coefficient of windows. An economic efficiency database for the constructed alternatives was built; the target building was set and the Passive ECM List for the target building was derived. The energy consumption evaluation and economic evaluation were performed for each of the constructed alternatives, and a methodology for guiding energy efficiency decisions was proposed based on the performance evaluation results, and the optimal Passive ECM List for the target building was derived.

Ground heat accumulation caused by imbalanced heating and cooling loads in a building can cause the heat-source temperature to increase as the operating age of a geothermal heat pump (GHP) system increases. An alternative system to improve upon this situation is the hybrid GHP system. This study reviews existing research on GHP systems and hybrid GHP systems, variable water flow (VWF) control, and coefficient of performance (COP) prediction. Generally, constant flow control is applied to the circulating pump to provide a flow rate according to the maximum load. The need for VWF control was identified because the hybrid GHP system is used mainly as a heating and cooling heat source system for partial loads rather than the entire building load. Previous studies on predicting the COPs of GHP systems developed prediction models by selecting input values based on mathematical models, collecting data through multiple measurement points, and utilizing data from production environments. The model can be limited by the field environment, and it is necessary to predict the COP using machine learning based on existing field monitoring data.

In a heat pump system, performance is an important indicator that should be monitored for system optimization, fault diagnosis, and operational efficiency improvement. Real-time performance measurement and monitoring during heat pump operation is difficult because expensive performance measurement devices or additional installation of various monitoring sensors required for performance calculation are required. When using a data-based machine-learning model, it is possible to predict and monitor performance by finding the relationship between input and output values through an existing sensor. In this study, the performance prediction model of the air-cooled heat pump system was developed and verified using artificial neural network, support vector machine, random forest, and K-nearest neighbor model. The operation data of the heat pump system installed in the university laboratory was measured and a prediction model for each machine-learning stage was developed. The mean bias error analysis is −3.6 for artificial neural network, −5 for artificial neural network, −7.7 for random forest, and −8.3 for K-nearest neighbor. The artificial neural network model with the highest accuracy and the shortest calculation time among the developed prediction models was applied to the Building Automation System to enable real-time performance monitoring and to confirm the field applicability of the developed model.

The installation and operation of geothermal systems increased due to the expectation of good cooling and heating performance due to stable heat source temperatures. In actual geothermal system operations, heat source temperature rises or falls due to an imbalance of heating and cooling energy usage. Problems of source side temperature result in reduced geothermal system performance. The purpose of this study is to develop hybrid geothermal system operation technology to stabilize temperature and improve system performance by utilizing auxiliary heat source system. The auxiliary heat source system is operated by comparing the performance when operating the geothermal heat pump system alone and the performance when operating the hybrid geothermal heat pump system. The performance of a hybrid geothermal system is determined by the circulating water temperature of the geothermal system and the circulating water temperature of the auxiliary heat source system. Hybrid geothermal heat pump system performance is predicted through numerical analysis and collection of hybrid geothermal system performance data at various temperature ranges through field test. An operating method was developed using the predicted performance as the changeover operating point of the hybrid geothermal heat pump system. When applying the development and operation technology, it handled about 11% more load than the existing geothermal system operation. The addition of an auxiliary heat source increases the initial investment cost compared to the existing geothermal system, but decreases energy consumption, confirming that the initial investment cost of 15.3 years is recovered.

AT-rich interactive domain 1A (ARID1A) is one of the most frequently mutated genes in hepatocellular carcinoma (HCC), but its clinical significance is not clarified. We aimed to evaluate the clinical significance of low ARID1A expression in HCC. By analyzing the gene expression data of liver from Arid1a-knockout mice, hepatic Arid1a-specific gene expression signature was identified (p < 0.05 and 0.5-fold difference). From this signature, a prediction model was developed to identify tissues lacking Arid1a activity and was applied to gene expression data from three independent cohorts of HCC patients to stratify patients according to ARID1A activity. The molecular features associated with loss of ARID1A were analyzed using The Cancer Genome Atlas (TCGA) multi-platform data, and Ingenuity Pathway Analysis (IPA) was done to uncover potential signaling pathways associated with ARID1A loss. ARID1A inactivation was clinically associated with poor prognosis in all three independent cohorts and was consistently related to poor prognosis subtypes of previously reported gene signatures (highly proliferative, hepatic stem cell, silence of Hippo pathway, and high recurrence signatures). Immune activity, indicated by significantly lower IFNG6 and cytolytic activity scores and enrichment of regulatory T-cell composition, was lower in the ARID1A-low subtype than ARID1A-high subtype. Ingenuity pathway analysis revealed that direct upstream transcription regulators of the ARID1A signature were genes associated with cell cycle, including E2F group, CCND1, and MYC, while tumor suppressors such as TP53, SMAD3, and CTNNB1 were significantly inhibited. ARID1A plays an important role in immune activity and regulating multiple genes involved in HCC development. Low-ARID1A subtype was associated with poor clinical outcome and suggests the possibility of ARID1A as a prognostic biomarker in HCC patients.

Accurate measurement of air flow rate is essential in automatic building control using the variable air volume (VAV) system. In order to solve the problems of the existing air flow measurement method and improve the accuracy of air flow control, this study developed a data-based multiple regression air flow prediction model. The independent variables used in the development of the predictive model were selected as the factors used for control and monitoring when operating with variable air flow rate in the existing air conditioning system. Data collection and correlation between independent variables and air flow rate of the terminal unit were analyzed. Using the IBM SPSS statistics version 25, an air flow rate prediction model was developed using multiple regression analysis. Reliability of model was evaluated by comparing the measured airflow. The relative error of −9.3% to 10.4% is shown when comparing the estimated air flow rate by the developed model with the measured air flow rate.

As the global energy trend continues, the importance of energy savings and efficient use is being emphasized, and the installation and operation of geothermal heat pump systems is increasing. In many buildings, where an actual geothermal heat pump system has been installed, problems of efficiency deterioration occur frequently because of the inefficient operation after installation of the heat pump system. The purpose of this study was to develop and verify the operating method for energy saving and performance improvement of multiple geothermal systems. A coefficient of performance (COP) prediction model using an artificial neural network for real-time COP predictions was developed. The operating method of a multi-geothermal heat pump system using a variable water flow rate control method and COP prediction model was developed. The geothermal heat pump system operates sequentially depending on the water flow rate of the circulation pump. The COP prediction model enabled real-time performance prediction during system operation. The circulation water flow rate was reduced by up to 29% compared to the existing operating method. Approximately 23% of the energy was saved. The COP system, including the consumption power of the circulation pump, was improved.

As policies for energy efficiency of buildings are being actively implemented, building energy performance improvement is urgently required. However, in Korea, information on measures and technologies for building energy efficiency is dispersed and concrete methods are not established, making it difficult to apply effective measures. Therefore, it is required to apply and evaluate energy efficiency measures through database construction integrating diverse information. In this study, the energy efficiency measures in the architectural sector that satisfy domestic legal standards are built. Because of the economic evaluation is necessary for the constructed alternatives, an economic efficiency database was established. The target building was set up, and energy efficiency measures were derived. In addition, a methodology that can induce energy efficient decision making of buildings was proposed, and the energy use evaluation and the economic analysis for each of the alternatives derived from applying the methodology to the target building were carried out. Furthermore, the optimal energy efficiency measures for the target building were suggested through the application of the decision-making process.

Acinetobacter baumannii is an aerobic and gram-negative pathogenic bacterium that is resistant to most antibiotics. Recently, A. baumannii 1656-2 exhibited the ability to form biofilms under clinical conditions. In this study, global metabolite profiling of both planktonic and biofilm forms of A. baumannii 1656-2 was performed using high-resolution nuclear magnetic resonance (NMR) spectroscopy and multivariate statistical analysis to investigate the metabolic patterns leading to biofilm formation. Principal components analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) score plots showed a distinct separation between planktonic and biofilm cells. Metabolites including acetates, pyruvate, succinate, UDP-glucose, AMP, glutamate, and lysine were increasingly involved in the energy metabolism of biofilm formation. In particular, the ratio of N-acetyl-D-glucosamine (GlcNAc) to D-glucosamine (GlcNH2) was significantly higher during biofilm formation than under the planktonic condition. This study demonstrates that NMR-based global metabolite profiling of bacterial cells can provide valuable insight into the metabolic changes in multidrug resistant and biofilm-forming bacteria such as A. baumannii 1656-2.

Gram-negative bacteria produce extracellular outer membrane vesicles (OMVs) that interact with host cells. Unlike Gram-negative bacteria, less is known about the production and role of extracellular membrane vesicles (MVs) in Gram-positive bacteria. The food-borne pathogen Listeria monocytogenes can survive under extreme environmental and energy stress conditions and the transcription factor σ(B) is involved in this survival ability. Here, we first determined the production of MVs from L. monocytogenes and evaluated whether general stress transcription factor σ(B) affected production of MVs in L. monocytogenes. L. monocytogenes secreted MVs during in vitro broth culture. The wild-type strain actively produced MVs approximately nine times more and also produced more intact shapes of MVs than those of the isogenic ΔsigB mutant. A proteomic analysis showed that 130 and 89 MV proteins were identified in the wild-type and ΔsigB mutant strains, respectively. Wild-type strain-derived MVs contained proteins regulated by σ(B) such as transporters (OpuCA and OpuCC), stress response (Kat), metabolism (LacD), translation (InfC), and cell division protein (FtsZ). Gene Ontology (GO) enrichment analysis showed that wild-type-derived MV proteins corresponded to several GO terms, including response to stress (heat, acid, and bile resistance) and extracellular polysaccharide biosynthetic process, but not the ΔsigB mutant. Internalin B (InlB) was almost three times more contained in MVs derived from the wild-type strain than in MVs derived from the ΔsigB mutant. Taken together, these results suggest that σ(B) plays a pivotal role in the production of MVs and protein profiles contained in MVs. L. monocytogenes MVs may contribute to host infection and survival ability under various stressful conditions.