Compound C inhibits the replication of feline coronavirus.

Feline Coronavirus (FCoV) is a viral pathogen of cats and a highly contagious virus. Cats in a cattery can be infected by up to 100%, and even household cats are infected by 20-60%. Some strains of FCoV are known to induce a fatal disease in cats named Feline Infectious Peritonitis (FIP). However, no effective treatments are available. We demonstrated that compound C (dorsomorphin) can potentially inhibit feline coronavirus replication. Compound C treatment decreased the FCoV-induced plaque formation and cytopathic effect in FCoV-infected cells. Compound C treatment also significantly reduced the amount of viral RNA and viral protein in the cells in a dose-dependent manner. Our findings suggest that compound C is potentially useful for feline coronavirus-related diseases.

Dietary exposure of the water flea Daphnia galeata to microcystin-LR.

Harmful substances like the cyanotoxin microcystin-leucine-arginine (MC-LR) are commonly found in eutrophic freshwater environments, posing risks to aquatic organisms. The water flea, Daphnia, is a well-established model organism for environmental toxicology research. Nevertheless, there is currently insufficient research on the genes that respond to MC-LR in Daphnia galeata. This study aimed to gain insights into the notable genes that react significantly to MC-LR. In this study, we generated an extensive RNA-Seq sequences isolated from the D. galeata HK strain, Han River in Korea. This strain was nourished with a diet of the green microalga Chlorella vulgaris and treated with pure MC-LR at a concentration of 36 ug/L. The transcriptome profile in response to the MC-LR treatment was obtained and 336 differentially expressed genes were subjected to Gene Ontology (GO) and euKaryotic Orthologous Groups of proteins analyses. GO enrichment analysis showed that chemical stimulus, amino sugar metabolic and catabolic process, oxidative stress, and detoxification were highly enriched, in reverse, proteolysis and fucosylation were underpresented. Detoxification process related genes such as peroxidase-like, chorion, and thyroid peroxidase-like were enriched for eliminating or neutralizing MC_LR from an organism's body. Furthermore, functional protein classification revealed an upregulation of lipid and inorganic ion transport processes, while amino acid and carbohydrate transport processes were found to be downregulated. These findings offer insights into how organisms respond to ecotoxic stimuli, providing valuable information for understanding adaptation or defense pathways.

AMPK inhibitor, compound C, inhibits coronavirus replication in vitro.

The coronavirus disease (COVID-19) pandemic has resulted in more than six million deaths by October 2022. Vaccines and antivirals for severe acute respiratory syndrome coronavirus 2 are now available; however, more effective antiviral drugs are required for effective treatment. Here, we report that a potent AMP-activated protein kinase (AMPK) inhibitor, compound C/dorsomorphin, inhibits the replication of the human coronavirus OC43 strain (HCoV-OC43). We examined HCoV-OC43 replication in control and AMPK-knockout (KO) cells and found that the virus replication decreased in AMPK-KO cells. Next, we examined the effect of the AMPK inhibitor, compound C on coronavirus replication. Compound C treatment efficiently inhibited the replication and decreased the coronavirus-induced cytotoxicity, further inhibiting autophagy. In addition, treatment with compound C in combination with chloroquine synergistically inhibited coronavirus replication. These results suggest that compound C can be considered as a potential drug candidate for COVID-19.

Hybrid model for daily streamflow and phosphorus load prediction.

Environmental factors, such as climate change and land use changes, affect water quality drastically. To consider these, various predictive models, both process-based and data-driven, have been used. However, each model has distinct limitations. In this study, a hybrid model combining the soil and water assessment tool and the reverse time attention mechanism (SWAT-RETAIN) was proposed for predicting daily streamflow and total phosphorus (TP) load of a watershed. SWAT-RETAIN was applied to Hwangryong River, South Korea. The hybrid model uses the SWAT output as input data for the RETAIN. Spatial, meteorological, and hydrological data were collected to develop the SWAT to generate high temporal resolution data. RETAIN facilitated effective simultaneous prediction. The SWAT-RETAIN exhibited high accuracy in predicting streamflow (Nash-Sutcliffe efficiency (NSE): 0.45, root mean square error (RMSE): 27.74, percent bias (PBIAS): 22.63 for test sets), and TP load (NSE: 0.50, RMSE: 423.93, PBIAS: 22.09 for test sets). This result was evident in the performance evaluation using flow duration and load duration curves. The SWAT-RETAIN provides enhanced temporal resolution and performance, enabling the simultaneous prediction of multiple variables. It can be applied to predict various water quality variables in larger watersheds.

Assessing the impacts of dam/weir operation on streamflow predictions using LSTM across South Korea.

Recently, weather data have been applied to one of deep learning techniques known as "long short-term memory (LSTM)" to predict streamflow in rainfall-runoff relationships. However, this approach may not be suitable for regions with artificial water management structures such as dams and weirs. Therefore, this study aims to evaluate the prediction accuracy of LSTM for streamflow depending on the availability of dam/weir operational data across South Korea. Four scenarios were prepared for 25 streamflow stations. Scenarios #1 and #2 used weather data and weather and dam/weir operational data, respectively, with the same LSTM model conditions for all stations. Scenarios #3 and #4 used weather data and weather and dam/weir operational data, respectively, with the different LSTM models for individual stations. The Nash-Sutcliffe efficiency (NSE) and the root mean squared error (RMSE) were adopted to assess the LSTM's performance. The results indicated that the mean values of NSE and RMSE were 0.277 and 292.6 (Scenario #1), 0.482 and 214.3 (Scenario #2), 0.410 and 260.7 (Scenario #3), and 0.592 and 181.1 (Scenario #4), respectively. Overall, the model performance was improved by the addition of dam/weir operational data, with an increase in NSE values of 0.182-0.206 and a decrease in RMSE values of 78.2-79.6. Surprisingly, the degree of performance improvement varied according to the operational characteristics of the dam/weir, and the performance tended to increase when the dam/weir with high frequency and great amount of water discharge was included. Our findings showed that the overall LSTM prediction of streamflow was improved by the inclusion of dam/weir operational data. When using dam/weir operational data to predict streamflow using LSTM, understanding of their operational characteristics is important to obtain reliable streamflow predictions.

Identifying the acute toxicity of contaminated sediments using machine learning models.

Ecological risk assessment of contaminated sediment has become a fundamental component of water quality management programs, supporting decision-making for management actions or prompting additional investigations. In this study, we proposed a machine learning (ML)-based approach to assess the ecological risk of contaminated sediment as an alternative to existing index-based methods and costly toxicity testing. The performance of three widely used index-based methods (the pollution load index, potential ecological risk index, and mean probable effect concentration) and three ML algorithms (random forest, support vector machine, and extreme gradient boosting [XGB]) were compared in their prediction of sediment toxicity using 327 nationwide data sets from Korea consisting of 14 sediment quality parameters and sediment toxicity testing data. We also compared the performances of classifiers and regressors in predicting the toxicity for each of RF, SVM, and XGB algorithms. For all algorithms, the classifiers poorly classified toxic and non-toxic samples due to limited information on the sediment composition and the small training dataset. The regressors with a given classification threshold provided better classification, with the XGB regressor outperforming the other models in the classification. A permutation feature importance analysis revealed that Cr, Cu, Pb, and Zn were major contributors to toxicity prediction. The ML-based approach has the potential to be even more useful in the future with the expected increase in available sediment data.

CTRP1 Knockout Attenuates Tumor Progression in A549 and HCT116 Cancer Cells.

C1q and TNF-related 1 (C1QTNF1/CTRP1) is an adiponectin-associated protein belonging to the C1q/TNF-related protein family. Recent studies have shown that the C1q and TNF-related protein (CTRP) family is involved in cancer progression; however, the specific role of CTRP1 in tumor progression has not yet been elucidated. To examine the role of CTRP1 in tumor progression, we generated CTRP1 knockout A549 and HCT116 cell lines, which reduced the expression levels of nuclear factor (NF)-κB-dependent and metastasis-promoting transcripts. We demonstrated that CTRP1 knockout inhibited the cell proliferation and invasion and tumor growth. Finally, database analysis showed that CTRP1 expression was upregulated in metastatic cancers and elevated levels of CTRP1 were associated with poor prognosis. These results suggest that CTRP1 expression contributes to NF-κB signaling and promotes tumor progression.

Coronavirus enzyme inhibitors-experimentally proven natural compounds from plants.

Coronavirus disease (COVID-19) can cause critical conditions that require efficient therapeutics. Several medicines are derived from plants, and researchers are seeking natural compounds to ameliorate the symptoms of COVID-19. Viral enzymes are popular targets of antiviral medicines; the genome of coronaviruses encodes several enzymes, including RNA-dependent RNA polymerase and viral proteases. Various screening systems have been developed to identify potential inhibitors. In this review, we describe the natural compounds that have been shown to exert inhibitory effects on coronavirus enzymes. Although computer-aided molecular structural studies have predicted several antiviral compound candidates, the current review focuses on experimentally proven natural compounds.

Educational applications of metaverse: possibilities and limitations.

This review aims to define the 4 types of the metaverse and to explain the potential and limitations of its educational applications. The metaverse roadmap categorizes the metaverse into 4 types: augmented reality, lifelogging, mirror world, and virtual reality. An example of the application of augmented reality in medical education would be an augmented reality T-shirt that allows students to examine the inside of the human body as an anatomy lab. Furthermore, a research team in a hospital in Seoul developed a spinal surgery platform that applied augmented reality technology. The potential of the metaverse as a new educational environment is suggested to be as follows: a space for new social communication; a higher degree of freedom to create and share; and the provision of new experiences and high immersion through virtualization. Some of its limitations may be weaker social connections and the possibility of privacy impingement; the commission of various crimes due to the virtual space and anonymity of the metaverse; and maladaptation to the real world for students whose identity has not been established. The metaverse is predicted to change our daily life and economy beyond the realm of games and entertainment. The metaverse has infinite potential as a new social communication space. The following future tasks are suggested for the educational use of the metaverse: first, teachers should carefully analyze how students understand the metaverse; second, teachers should design classes for students to solve problems or perform projects cooperatively and creatively; third, educational metaverse platforms should be developed that prevent misuse of student data.

Epigallocatechin Gallate (EGCG), a Green Tea Polyphenol, Reduces Coronavirus Replication in a Mouse Model.

The COVID-19 pandemic has resulted in a huge number of deaths from 2020 to 2021; however, effective antiviral drugs against SARS-CoV-2 are currently under development. Recent studies have demonstrated that green tea polyphenols, particularly EGCG, inhibit coronavirus enzymes as well as coronavirus replication in vitro. Herein, we examined the inhibitory effect of green tea polyphenols on coronavirus replication in a mouse model. We used epigallocatechin gallate (EGCG) and green tea polyphenols containing more than 60% catechin (GTP60) and human coronavirus OC43 (HCoV-OC43) as a surrogate for SARS-CoV-2. Scanning electron microscopy analysis results showed that HCoV-OC43 infection resulted in virion particle production in infected cells. EGCG and GTP60 treatment reduced coronavirus protein and virus production in the cells. Finally, EGCG- and GTP60-fed mice exhibited reduced levels of coronavirus RNA in mouse lungs. These results demonstrate that green tea polyphenol treatment is effective in decreasing the level of coronavirus in vivo.

LNX1 Contributes to Cell Cycle Progression and Cisplatin Resistance.

The ligand of numb-protein X1 (LNX1) acts as a proto-oncogene by inhibiting p53 stability; however, the regulation of LNX1 expression has not been investigated. In this study, we screened chemicals to identify factors that potentially regulate LNX1 expression. We found that LNX1 expression levels were decreased by DNA damage, including that by cisplatin. Upon treatment with lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA), LNX1 expression levels increased. In addition, cell-cycle progression increased upon LNX1 expression; the levels of S and G2/M populations were correlated with LNX1 expression. Moreover, in CRISPR-Cas9-mediated LNX1 knockout cells, we observed a delay in cell-cycle progression and a downregulation of genes encoding the cell-cycle markers cyclin D1 and cyclin E1. Finally, the upregulation of LNX1-activated cell-cycle progression and increased resistance to cisplatin-mediated cell death. Taken together, these results suggest that LNX1 contributes to cell-cycle progression and cisplatin resistance.

Elevated Levels of CTRP1 in Obesity Contribute to Tumor Progression in a p53-Dependent Manner.

Mounting evidence supports the relationship between obesity and cancer. However, the molecular mechanisms linking obesity with cancer remain largely uninvestigated. In this study, we demonstrate that the expression of C1q/TNF-related protein 1 (CTRP1), an adiponectin paralogue, contributes to tumor growth by regulating the tumor suppressor p53. In our study, obese mice on a high-fat diet showed higher serum CTRP1 levels. Through in vitro experiments, we showed that the secreted form of CTRP1 in the culture medium decreased p53 expression and p53-dependent transcription in the cells. Moreover, CTRP1 treatment enhanced colony formation and cell migration. These results collectively suggest that elevated levels of CTRP1 in obesity significantly contribute to tumor progression.

Comparison of Intracardiac Echocardiography and Transesophageal Echocardiography for Image Guidance in Percutaneous Patent Foramen Ovale Closure.

Background and Objectives: Transesophageal echocardiography (TEE) guidance is the current gold standard for catheter-based procedures in the treatment of structural heart diseases. Intracardiac echocardiography (ICE), which can be performed under local anesthesia, has been recently introduced and is becoming more widely used. We aimed to compare the efficacy and safety of ICE and TEE in patent foramen ovale (PFO) device closure. Materials and Methods: All 74 patients with a history of cryptogenic stroke undergoing PFO closure for secondary prophylaxis were selected from our registry. Intraprocedural TEE was performed by echocardiographer-cardiologists with the patient under general anesthesia. Conversely, ICE was performed with the patient under local anesthesia. Baseline characteristics, procedural details, and immediate outcomes were compared between the TEE and ICE groups (n = 49 and n = 25, respectively). Results: Although patients in the ICE group were older (47 ± 10 vs. 57 ± 7 years, p < 0.001), sex and comorbidity variables were similar between the two groups. The degree of inducible right-to-left shunt via the PFO, assessed using preprocedural TEE, was also comparable. Notably, fluoroscopy time (22 ± 18 vs. 16 ± 7 min, p = 0.030), radiation dose (498 ± 880 vs. 196 ± 111 mGy, p = 0.022), and total procedural time in the catheter laboratory (99 ± 30 vs. 67 ± 12 min, p < 0.001) were significantly lower in the ICE group than those in the TEE group. The entire hospital stay was similar between groups (3.8 ± 2.2 vs. 3.4 ± 1.3 days, p = 0.433). No procedural complications, such as device embolization, pericardial hemorrhage, major bleeding, mortality, or access-related vascular injury were reported in either group. Conclusions: ICE-guided PFO device closure is quicker and less hazardous in terms of radiation exposure than the TEE-guided procedure, with similar procedural outcomes and duration of hospital stay.

Risk Factors for Closure Failure following Percutaneous Transfemoral Transcatheter Aortic Valve Implantation.

BACKGROUND: The percutaneous access site of transfemoral transcatheter aortic valve implantation (TAVI) procedures is commonly closed using a preclosure technique with suture-type closure devices. We sought to evaluate the predictors and outcomes of percutaneous closure device (PCD) failure during transfemoral TAVI. METHODS AND RESULTS: This single-center retrospective analysis included 184 patients who underwent transfemoral TAVI using 2 ProGlide sutures for severe aortic stenosis between July 2011 and September 2018. PCD failure was observed in 11.4%. The causes of PCD failure included 5 cases of insufficient hemostasis, 13 cases of arterial stenosis or occlusion, and 3 cases of dissection. Closure failures were managed by surgical repair in 10 patients and endovascular treatment in 11 patients. In a multivariate binary logistic model, a minimum lumen diameter of the common femoral artery (CFA) (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.15-0.83, P = 0.017) and left femoral access (OR 2.89, 95% CI 1.01-8.30, P = 0.048) was identified as a predictor of PCD failure. PCD failure was not associated with increased mortality (0% vs. 2.5%, P = 1.000) or a major adverse cardiovascular event (MACE; 4.8% vs. 4.3%, P = 1.000) at 30 days. CONCLUSIONS: PCD failures were not uncommon in patients undergoing percutaneous transfemoral TAVI. Small CFA diameter and left femoral access are predictors of PCD failure. However, PCD failures were not associated with increased mortality or MACE.

Frequent premature ventricular complex is associated with left atrial enlargement in patients with normal left ventricular ejection fraction.

BACKGROUND: Premature ventricular complex (PVC) has been regarded as benign; however, when frequent, the arrhythmia can induce left ventricular (LV) systolic dysfunction. Meanwhile, the influence of PVCs on cardiac structural remodeling and functional change before occurrence of overt systolic heart failure has not been fully described. In this study, we attempted to identify early cardiac structural/functional manifestations of frequent PVCs in patients with normal LV systolic function. METHODS: A total of 146 patients (age: 55 ± 15 years, 48 males) with frequent PVCs observed on 24-hour Holter monitoring (>10/h) and normal LV ejection fraction (LV EF ≥ 55% on echocardiography) were enrolled. Clinical characteristics and echocardiographic parameters of the patients were compared with those of an age-/sex-matched control group (n = 292, age: 55 ± 15 years, 96 males). RESULTS: Patients with frequent PVCs had significantly larger left atrial volume index (LAVI [28 ± 9 mL/m(2) vs. 24 ± 7 mL/m(2) ]), along with larger LV end-diastolic dimension (49.4 ± 4.4 mm vs. 48.5 ± 3.9 mm), lower LV EF (63 ± 7% vs. 66 ± 6%), and lower peak systolic mitral annular velocity (7 ± 2 cm/s vs. 8 ± 2 cm/s; P < 0.05 for all), whereas other clinical characteristics were similar. In particular, in patients with frequent PVCs, LAVI showed linear correlation with PVC burden (R = 0.30, P < 0.001), and, in a multiple regression model, PVC burden independently estimated LAVI, even after controlling for age, sex, comorbidities, and systolic function (ß = 0.309, P < 0.001). CONCLUSION: Frequent PVC is associated with LA enlargement in patients with normal LV EF. Atrial anatomical remodeling may precede LV geometry change and systolic dysfunction in patients with frequent PVCs.

Predictors of recovery of left ventricular systolic dysfunction after acute myocardial infarction: from the korean acute myocardial infarction registry and korean myocardial infarction registry.

BACKGROUND AND OBJECTIVES: We investigated the predictors of the recovery of depressed left ventricular ejection fraction (LVEF) in patients with moderate or severe left ventricular (LV) systolic dysfunction after acute myocardial infarction (MI). SUBJECTS AND METHODS: We analyzed 1307 patients, who had moderately or severely depressed LVEF (<45%) on echocardiography soon after acute MI and who underwent a follow-up echocardiography, among 27369 patients from the Korea Working Group on the Myocardial Infarction Registry. Patients were categorized into two groups according to recovery of LVEF: group I with consistently depressed LVEF (<45%) at the follow-up echocardiography and group II with a recovery of LVEF (≥45%). RESULTS: Recovery of LV systolic dysfunction was observed in 51% of the subjects (group II, n=663; ΔLVEF, 16.2±9.3%), whereas there was no recovery in the remaining subjects (group I, n=644; ΔLVEF, 0.6±7.1%). In the multivariate analysis, independent predictors of recovery of depressed LVEF were as follows {odds ratio (OR) [95% confidence interval (CI)]}: moderate systolic dysfunction {LVEF ≥30% and <45%; 1.73 (1.12-2.67)}, Killip class I-II {1.52 (1.06-2.18)}, no need for diuretics {1.59 (1.19-2.12)}, non-ST-segment elevation MI {1.55 (1.12-2.16)}, lower peak troponin I level {<24 ng/mL, median value; 1.55 (1.16-2.07)}, single-vessel disease {1.53 (1.13-2.06)}, and non-left anterior descending (LAD) culprit lesion {1.50 (1.09-2.06)}. In addition, the use of statin was independently associated with a recovery of LV systolic dysfunction {OR (95% CI), 1.46 (1.07-2.00)}. CONCLUSION: Future contractile recovery of LV systolic dysfunction following acute MI was significantly related with less severe heart failure at the time of presentation, a smaller extent of myonecrosis, or non-LAD culprit lesions rather than LAD lesions.

Deposition of Cryptosporidium parvum oocysts in porous media: a synthesis of attachment efficiencies measured under varying environmental conditions.

An extensive set of column experiments was performed with freshly harvested Cryptosporidium parvum oocysts to evaluate the effects of solution chemistry, surface coatings, interactions with other suspended particles, and pore fluid velocity on the fate and transport of this widely occurring waterborne pathogen in sandy porous media. We synthesized our data set with a comprehensive literature survey of similar experiments, to compute attachment (collision) efficiencies (α) used in colloid filtration theory (CFT) using three models for the single collector efficiency (η) across a wide range of experimental conditions. Most prior experiments have observed the transport of surface-treated, sterile C. parvum oocyst in porous media. Our column data confirm for freshly harvested oocysts that the presence of iron coatings on the sand medium and the presence of suspended illite clay drastically enhance oocyst deposition. Increasing ionic strength and decreasing pH also systematically enhance the attachment efficiency. Attachment efficiency decreases only at a very high ionic strength, most likely as a result of steric repulsion and possibly other changes in oocyst surface properties. Attachment efficiencies vary with fluid flow rate but without showing specific trends. We found that the computed attachment efficiency across all reported experiments could be reliably estimated using a regression model based on parameters related to ionic strength and pH. The regression model performed better with the Nelson-Ginn η model and Tufenkji-Elimelech η model than with the Rajagopalan-Tien η model. When CFT is used in environmental assessments, the proposed regression model provides a practical estimator for attachment efficiencies of C. parvum oocyst deposition in porous media for a variety of environmental conditions unfavorable to attachment.

Role of FDG-PET/CT in detecting lymphomatous bone marrow involvement in patients with newly diagnosed diffuse large B-cell lymphoma.

To evaluate the role of FDG-PET/CT in detecting bone marrow (BM) involvement, pre-treatment bilateral bone marrow biopsies (BMBs) and FDG-PET/CT scans of 89 patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab-CHOP were reviewed and analyzed. Fourteen patients (15.7%) had lymphomatous involvement based on BMB (BMB+), and 17 patients (19.1%) had the possibility of BM involvement on FDG-PET/CT (FDG-PET/CT+). Seventy-two patients (80.8%) had concordant results between BMB and FDG-PET/CT (seven patients were positive for both, and 65 patients were negative for both), but 17 patients (19.2%) had a discordant interpretation (seven patients were BMB+ and FDG-PET/CT-, and ten were BMB- and FDG-PET/CT+). Although BMB+ patients had an inferior 2-year EFS (37.0% vs. 79.8%, p < 0.001) and OS (36.3% vs. 81.0%, p < 0.001) compared to BMB- patients, no differences in EFS (62.6% vs. 72.7%, p = 0.185) and OS (59.4% vs. 78.0%, p = 0.146) were shown between FDG-PET/CT+ and FDG-PET/CT- patients. Whereas six of seven patients with diffuse hypermetabolism were BMB+, only one of ten patients with focal hypermetabolism was BMB+. The results suggest that FDG-PET/CT had a limited value to detect BM involvement in patients with DLBCL. Focal hypermetabolism of hematopoietic BM in FDG-PET/CT had no impact on survival.

Autonomous real-time adaptive management of soil salinity using a receding horizon control algorithm: a pilot-scale demonstration.

Soil salinization is a potentially negative side effect of irrigation with reclaimed water. While optimization schemes have been applied to soil salinity control, these have typically failed to take advantage of real-time sensor feedback. This study incorporates current soil observation technologies into the optimal feedback-control scheme known as Receding Horizon Control (RHC) to enable successful autonomous control of soil salinization. RHC uses real-time sensor measurements, physically-based state prediction models, and optimization algorithms to drive field conditions to a desired environmental state by manipulating application rate or irrigation duration/frequency. A simulation model including the Richards equation coupled to energy and solute transport equations is employed as a state estimator. Vertical multi-sensor arrays installed in the soil provide initial conditions and continuous feedback to the control scheme. An optimization algorithm determines the optimal irrigation rate or frequency subject to imposed constraints protective of soil salinization. A small-scale field test demonstrates that the RHC scheme is capable of autonomously maintaining specified salt levels at a prescribed soil depth. This finding suggests that, given an adequately structured and trained simulation model, sensor networks, and optimization algorithms can be integrated using RHC to autonomously achieve water reuse and agricultural objectives while managing soil salinization.