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Background/Aims Atezolizumab plus bevacizumab (ATE+BEV) therapy has become the recommended first-line therapy for patients with unresectable hepatocellular carcinoma (HCC) because of favorable treatment responses. However, there is a lack of data on sequential regimens after ATE+BEV treatment failure. We aimed to investigate the clinical outcomes of patients with advanced HCC who received subsequent systemic therapy for disease progression after ATE+BEV. Methods This multicenter, retrospective study included patients who started second-line systemic treatment with sorafenib or lenvatinib after HCC progressed on ATE+BEV between August 2019 and December 2022. Treatment response was assessed using the Response Evaluation Criteria in Solid Tumors (version 1.1.). Clinical features of the two groups were balanced through propensity score (PS) matching. Results This study enrolled 126 patients, 40 (31.7%) in the lenvatinib group, and 86 (68.3%) in the sorafenib group. The median age was 63 years, and males were predominant (88.1%). In PS-matched cohorts (36 patients in each group), the objective response rate was similar between the lenvatinib- and sorafenib-treated groups (5.6% vs. 8.3%; P=0.643), but the disease control rate was superior in the lenvatinib group (66.7% vs. 22.2%; P

Background/Aims The global proportion of hepatocellular carcinoma (HCC) attributable to metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. The MAFLD diagnostic criteria allows objective diagnosis in the presence of steatosis plus defined markers of metabolic dysfunction, irrespective of concurrent liver disease. We aimed to determine the total global prevalence of MAFLD in HCC cohorts (total-MAFLD), including the proportion with MAFLD as their sole liver disease (single-MAFLD), and the proportion of those with concurrent liver disease where MAFLD was a contributary factor (mixed-MAFLD). Methods This systematic review and meta-analysis included studies systematically ascertaining MAFLD in HCC cohorts, defined using international expert panel criteria including ethnicity-specific BMI cut-offs. A comparison of clinical and tumour characteristics was performed between single-MAFLD, mixed-MAFLD, and non-MAFLD HCC. Results 22 studies (56,565 individuals with HCC) were included. Total and single-MAFLD HCC prevalence was 48.7% (95% confidence interval [CI] 34.5–63.0%) and 12.4% (95% CI 8.3–17.3%), respectively. In HCC due to chronic hepatitis B, C, and alcohol-related liver disease, mixed-MAFLD prevalence was 40.0% (95% CI 30.2–50.3%), 54.1% (95% CI 40.4–67.6%) and 64.3% (95% CI 52.7–75.0%), respectively. Mixed-MAFLD HCC had significantly higher likelihood of cirrhosis and lower likelihood of metastatic spread compared to single-MAFLD HCC, and a higher platelet count and lower likelihood of macrovascular invasion compared to non-MAFLD HCC. Conclusions MAFLD is common as a sole aetiology, but more so as a co-factor in mixed-aetiology HCC, supporting the use of positive diagnostic criteria.

Background & Aims: We investigated the association of physical activity (PA) levels and changes with the risk of hepatocellular carcinoma (HCC) in patients with type 2 diabetes. Methods: Patients with type 2 diabetes who had undergone health examinations in 2009 and 2011 were enrolled. In total, 1,439,152 patients were included in the analysis. The level of PA was classified as inactive (

ObjectiveThis study aims to assess the effect of mindfulness intervention on negative emotions (anxiety and depression) and quality of life in malignant tumor patients.MethodsThe databases, including CNKI, VIP, Wanfang, Chinese Biomedical Literature Database disc (CBMdisc), PubMed, Embase, Cochrane Library, and Web of Science (WoS), were searched from inception to January 2024. Randomized controlled trials examining the effects of mindfulness intervention on negative emotions and quality of life in malignant tumor patients were selected. Meta-analysis was conducted using RevMan 5.1.ResultsA total of 11 studies involving 993 patients were included. Compared with usual care, mindfulness intervention effectively reduced anxiety [SMD = −0.81, 95% CI (−1.01, −0.60), p

Background Administration of pancreatic endoplasmic reticulum kinase inhibitor (PERKi) improved insulin secretion and hyperglycemia in obese diabetic mice. In this study, autophagic balance was studied whether to mediate it. Methods Human islets were isolated from living patients without diabetes. PERKi GSK2606414 effects were evaluated in the islets under glucolipotoxicity by palmitate. Islet insulin contents and secretion were measured. Autophagic flux was assessed by microtubule associated protein 1 light chain 3 (LC3) conversion, a red fluorescent protein (RFP)-green fluorescent protein (GFP)- LC3 tandem assay, and P62 levels. For mechanical analyses, autophagy was suppressed using 3-methyladenine in mouse islets. Small interfering RNA for an autophagy-related gene autophagy related 7 (Atg7) was transfected to interfere autophagy. Results PERKi administration to mice decreased diabetes-induced P62 levels in the islets. Glucolipotoxicity significantly increased PERK phosphorylation by 70% and decreased insulin contents by 50% in human islets, and addition of PERKi (40 to 80 nM) recovered both. PERKi also enhanced glucose-stimulated insulin secretion (6-fold). PERKi up-regulated LC3 conversion suppressed by glucolipotoxicity, and down-regulated P62 contents without changes in P62 transcription, indicating enhanced autophagic flux. Increased autophagosome-lysosome fusion by PERKi was visualized in mouse islets, where PERKi enhanced Atg7 bound to LC3. Suppression of Atg7 eliminated PERKi-induced insulin contents and secretion. Conclusion This study provided functional changes of human islets with regard to autophagy under glucolipotoxicity, and suggested modulation of autophagy as an anti-diabetic mechanism of PERKi.

Abstract Background We examined the incidence and predictors of clinical outcomes in metabolic dysfunction‐associated fatty liver disease (MAFLD), focusing on anthropometric parameters. Methods Adult patients with MAFLD were identified in nationwide databases and a hospital cohort. Primary endpoints were atherosclerotic cardiovascular disease (ASCVD) and advanced fibrosis. Logistic and Cox regression analyses were used to analyse the association between anthropometric parameters and endpoints. Results In total, 4407 of 15 256 (28.9%) and 6274 of 25 784 subjects (24.3%) had MAFLD in the nationwide database; of these, 403 (9.2%) and 437 (7.0%) subjects were of lean/normal weight, respectively. Compared to the overweight/obese group, the lean/normal weight group had a significantly lower muscle mass (15.0 vs. 18.9 kg) and handgrip strength (31.9 vs. 35.1 kg) and had a higher ASCVD risk (9.0% vs. 6.3% and 15.9% vs. 8.5%; Ps

Most carcass and meat quality traits are moderate to highly heritable, indicating that they can be improved through selection. Genetic evaluation for these types of traits is performed using performance data obtained from commercial and progeny testing evaluation. The performance data from commercial farms are available in large volume, however, some drawbacks have been observed. The drawback of the commercial data is mainly due to sorting of animals based on live weight prior to slaughter, and this could lead to bias in the genetic evaluation of later measured traits such as carcass traits. The current study has two components to address the drawback of the commercial data. The first component of the study aimed to estimate genetic parameters for carcass and meat quality traits in Korean Hanwoo cattle using a large sample size of industry-based carcass performance records (n = 469,002). The second component of the study aimed to describe the impact of sorting animals into different contemporary groups based on an early measured trait and then examine the effect on the genetic evaluation of subsequently measured traits. To demonstrate our objectives, we used real performance data to estimate genetic parameters and simulated data was used to assess the bias in genetic evaluation. The results of our first study showed that commercial data obtained from slaughterhouses is a potential source of carcass performance data and useful for genetic evaluation of carcass traits to improve beef cattle performance. However, we observed some harvesting effect which leads to bias in genetic evaluation of carcass traits. This is mainly due to the selection of animal based on their body weight before arrival to slaughterhouse. Overall, the non-random allocation of animals into a contemporary group leads to a biased estimated breeding value in genetic evaluation, the severity of which increases when the evaluation traits are highly correlated.

The gut microbiota and microbial metabolites influence the enteric nervous system and the central nervous system via the microbial–gut–brain axis. Increasing body of evidence suggests that disturbances in the metabolism of peripheral branched-chain amino acids (BCAAs) can contribute to the development of neurodegenerative diseases through neuroinflammatory signaling. Preliminary research has shown that longitudinal changes in serum amino acid levels in mouse models of Parkinson’s disease (PD) are negatively correlated with disease progression. Therefore, the aim of the present study was to determine the changes in serum levels of short-chain fatty acids (SCFAs) in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD after dietary BCAA supplementation. In our research, gas chromatography–mass spectrometry was used to detect serum SCFA concentrations. The data were then analyzed with principal component analysis and orthogonal partial least squares discriminant analysis. Finally, the correlations of serum SCFA levels with gut and motor function in MPTP-induced PD mice were explored. Propionic acid, acetic acid, butyric acid, and isobutyric acid concentrations were elevated in MPTP + H-BCAA mice compared with MPTP mice. Propionic acid concentration was increased the most, while the isovaleric acid concentration was decreased. Propionic acid concentration was positively correlated with fecal weight and water content and negatively correlated with the pole-climbing duration. In conclusion, these results not only suggest that propionic acid may be a potential biomarker for PD, but also indicate the possibility that PD may be treated by altering circulating levels of SCFA.

Background: Carbapenemase-producing Enterobacterales (CPE) are global concerns in infection control, and the number of CPE outbreaks in hospitals is increasing despite the strengthening of contact precautions. This study aimed to confirm the prevalence and transition rate of CPE infection from stool surveillance culture and to identify the acquisition pathway of CPE. Methods: This is a longitudinal review of patients with stool surveillance cultures at a tertiary center in Seoul, South Korea, from July 2018 to June 2020. Pulsed-field gel electrophoresis, multi-locus sequence typing, and whole genome sequencing were performed for carbapenemase-producing Klebsiella pneumoniae and Escherichia coli strains. Results: Among 1620 patients who had undergone stool CPE surveillance cultures, only 7.1% of active surveillance at the Emergency Room (ER) and 4.4% of universal surveillance in the Intensive Care Unit (ICU) were stool CPE positive. The transition rates from stool carriers to clinical CPE infections were 29.4% in the ER and 31.3% in the ICU. However, it was significantly high (55.0%) in the initial stool CPE-negative ICU patients. Among the initial stool CPE-positive patients, hypertension (61% vs. 92.3%, P = 0.004), malignancy (28.8% vs. 53.8%, P = 0.027), and mechanical ventilation (25.4% vs. 53.8%, P = 0.011) were significant risk factors for clinical CPE infection. Molecular typing revealed that sequence type (ST) 307 and ST 395 were dominant in K. pneumoniae, and ST 410 was dominant in E. coli isolates. Conclusions: Active surveillance showed a higher detection rate than universal stool CPE screening, and one-third of positive stool CPE specimens ultimately developed subsquent clinical CPE infection. According to the molecular typing of the identified CPE strains, in-hospital spread prevailed over external inflow, and the transition rate to clinical CPE was particularly high in the ICU. Therefore, in order to control CPE propagation, not only active surveillance to block inflow from outside, but also continuous ICU monitoring within the hospital is necessary.

Abstract Background/Aims Regression of liver fibrosis during antiviral therapy in chronic hepatitis B (CHB) patients has been demonstrated, but data on the influence of long-term treatment with tenofovir disoproxil fumarate (TDF) on liver stiffness (LS) measured by transient elastography are scarce. We aimed to investigate the changes in LS values during the 144-week TDF therapy in treatment-naïve CHB patients. Methods This prospective observational study was conducted from April 2015 to July 2020 at CHA Bundang Medical Center. Laboratory tests and LS measurements were performed at baseline and repeated at weeks 12, 24, 48, 96, and 144. A significant decline in LS was defined as ≥ 30% decrease in LS value at week 96 from baseline. Results A total of 48 treatment-naïve CHB patients initiating TDF therapy were screened, and 36 patients were included in the final analysis (median age, 46 [interquartile range, 34.5–55.8] years; 19 men [52.8%]). During TDF therapy, the median LS values decreased from 13.8 kPa at baseline to 8.7 kPa, 6.5 kPa, and 6.4 kPa at weeks 48, 96, and 144, respectively (all P

Abstract Background Femoral torsion is primarily measured by computed tomography (CT), which has cost and radiation exposure concerns. Recently, femoral anteversion measurement by a simple radiograph-based mobile application was developed for patients with cerebral palsy. This study aimed to validate the use of a mobile application that can reconstruct a three-dimensional model of the femur from conventional radiographs for adults. Methods Medical records of 76 patients undergoing conventional femur anteroposterior/lateral radiography and femur CT were reviewed. To measure femoral anteversion on the reconstructed 3-dimensional images from both the mobile application and CT, we drew a line which connects the posterior margins of each femoral condyle and another line which passes through the center of the femoral head and the midpoint of the femoral neck. After the reliability test, a single examiner measured femoral anteversion on the mobile application and CT. Pearson’s correlation analysis was used to assess the correlation between anteversion on the mobile application and CT. Results Femoral anteversion measured on both CT and the mobile application showed excellent reliability (intraclass correlation coefficients: 0.808–0.910). The correlation coefficient between femoral anteversion measured using CT and the mobile application was 0.933 (p

Abstract Hyperoxia is frequently used for treating acute respiratory failure, but it can cause acute lung injury. Nucleotide-binding domain and leucine-rich-repeat-containing family member X1 (NLRX1) is localized in mitochondria and involved in production of reactive oxygen species, inflammation, and apoptosis, which are the features of hyperoxic acute lung injury (HALI). The contribution of NLRX1 to HALI has not previously been addressed. Thus, to investigate the role of NLRX1 in hyperoxia, we generated a murine model of HALI in wild-type (WT) and NLRX1−/− mice by exposure to > 95% oxygen for 72 h. As a result, NLRX1 expression was elevated in mice exposed to hyperoxia. In acute lung injury, levels of inflammatory cells, protein leakage, cell cytotoxicity, and pro-inflammatory cytokines were diminished in NLRX1−/− mice compared to WT mice. In a survival test, NLRX1−/− mice showed reduced mortality under hyperoxic conditions, and apoptotic cell death and caspase expression and activity were also lower in NLRX1−/− mice. Furthermore, levels of the MAPK signaling proteins ERK 1/2, JNK, and p38 were decreased in NLRX1-deficient mice than in WT mice exposed to hyperoxia. The study shows that a genetic deficit in NLRX1 can suppress hyperoxia-induced apoptosis, suggesting that NLRX1 acts as a pivotal regulator of HALI.

Propagation of transgenic animals by germline transmission using assisted reproductive technologies such as in vitro fertilization (IVF) is the most efficient way to produce transgenic colonies for biomedical research. The objective of this study was to generate transgenic puppies from a founder dog expressing the mutated human amyloid precursor protein (mhAPP) gene. Experiment I assessed the characteristics of the semen prepared by freshly diluted, swim-up, and Percoll gradient methods using a computer-assisted semen analyzer (CASA). Motile and progressively motile sperm counts were higher in the Percoll gradient samples (p

The purpose of the current review was to explore and summarize different studies concerning the detection and characterization of candidate genes and genomic regions associated with economically important traits in Hanwoo beef cattle. Hanwoo cattle, the indigenous premium beef cattle of Korea, were introduced for their marbled fat, tenderness, characteristic flavor, and juiciness. To date, there has been a strong emphasis on the genetic improvement of meat quality and yields, such as backfat thickness (BFT), marbling score (MS), carcass weight (CW), eye muscle area (EMA), and yearling weight (YW), as major selection criteria in Hanwoo breeding programs. Hence, an understanding of the genetics controlling these traits along with precise knowledge of the biological mechanisms underlying the traits would increase the ability of the industry to improve cattle to better meet consumer demands. With the development of high-throughput genotyping, genomewide association studies (GWAS) have allowed the detection of chromosomal regions and candidate genes linked to phenotypes of interest. This is an effective and useful tool for accelerating the efficiency of animal breeding and selection. The GWAS results obtained from the literature review showed that most positional genes associated with carcass and growth traits in Hanwoo are located on chromosomes 6 and 14, among which LCORL, NCAPG, PPARGC1A, ABCG2, FAM110B, FABP4, DGAT1, PLAG1, and TOX are well known. In conclusion, this review study attempted to provide comprehensive information on the identified candidate genes associated with the studied traits and genes enriched in the functional terms and pathways that could serve as a valuable resource for future research in Hanwoo breeding programs.

This paper introduces an approach to the automated measurement and analysis of dairy cows using 3D point cloud technology. The integration of advanced sensing techniques enables the collection of non-intrusive, precise data, facilitating comprehensive monitoring of key parameters related to the health, well-being, and productivity of dairy cows. The proposed system employs 3D imaging sensors to capture detailed information about various parts of dairy cows, generating accurate, high-resolution point clouds. A robust automated algorithm has been developed to process these point clouds and extract relevant metrics such as dairy cow stature height, rump width, rump angle, and front teat length. Based on the measured data combined with expert assessments of dairy cows, the quality indices of dairy cows are automatically evaluated and extracted. By leveraging this technology, dairy farmers can gain real-time insights into the health status of individual cows and the overall herd. Additionally, the automated analysis facilitates efficient management practices and optimizes feeding strategies and resource allocation. The results of field trials and validation studies demonstrate the effectiveness and reliability of the automated 3D point cloud approach in dairy farm environments. The errors between manually measured values of dairy cow height, rump angle, and front teat length, and those calculated by the auto-measurement algorithm were within 0.7 cm, with no observed exceedance of errors in comparison to manual measurements. This research contributes to the burgeoning field of precision livestock farming, offering a technological solution that not only enhances productivity but also aligns with contemporary standards for sustainable and ethical animal husbandry practices.

The rapid evolution of 3D technology in recent years has brought about significant change in the field of agriculture, including precision livestock management. From 3D geometry information, the weight and characteristics of body parts of Korean cattle can be analyzed to improve cow growth. In this paper, a system of cameras is built to synchronously capture 3D data and then reconstruct a 3D mesh representation. In general, to reconstruct non-rigid objects, a system of cameras is synchronized and calibrated, and then the data of each camera are transformed to global coordinates. However, when reconstructing cattle in a real environment, difficulties including fences and the vibration of cameras can lead to the failure of the process of reconstruction. A new scheme is proposed that automatically removes environmental fences and noise. An optimization method is proposed that interweaves camera pose updates, and the distances between the camera pose and the initial camera position are added as part of the objective function. The difference between the camera’s point clouds to the mesh output is reduced from 7.5 mm to 5.5 mm. The experimental results showed that our scheme can automatically generate a high-quality mesh in a real environment. This scheme provides data that can be used for other research on Korean cattle.

Accurate weight measurement is critical for monitoring the growth and well-being of cattle. However, the traditional weighing process, which involves physically placing cattle on scales, is labor-intensive and stressful for the animals. Therefore, the development of automated cattle weight prediction techniques assumes critical significance. This study proposes a weight prediction approach for Korean cattle using 3D segmentation-based feature extraction and regression machine learning techniques from incomplete 3D shapes acquired from real farm environments. Firstly, we generated mesh data of 3D Korean cattle shapes using a multiple-camera system. Subsequently, deep learning-based 3D segmentation with the PointNet network model was employed to segment 3D mesh data into two dominant parts: torso and center body. From these segmented parts, the body length, chest girth, and chest width of Korean cattle were extracted. Finally, we implemented five regression machine learning models (CatBoost regression, LightGBM, polynomial regression, random forest regression, and XGBoost regression) for weight prediction. To validate our approach, we captured 270 Korean cattle in various poses, totaling 1190 poses of 270 cattle. The best result was achieved with mean absolute error (MAE) of 25.2 kg and mean absolute percent error (MAPE) of 5.85% using the random forest regression model.

Background: To investigate the clinical characteristics of Addison’s disease caused by adrenal tuberculosis in Tibet. After the anti-tuberculosis treatment, the clinical features between continuous glucocorticoid therapy and glucocorticoid withdrawal were analyzed. Methods: Clinical data of patients with Addison's disease caused by adrenal tuberculosis diagnosed in The People's Hospital of Tibet Autonomous Region from January 2015 to October 2021 were collected and analyzed. All patients were taking anti-tuberculosis and glucocorticoids replacement therapy, and the root cause of the disease was analyzed following prognosis observations. Results: There were 25 patients (24 Tibetan and 1 Han patient) with Addison's disease caused by adrenal tuberculosis, including 18 males and 7 females. A total of 21 cases were followed up successfully, of which 13 cases discontinued anti-tuberculosis drugs successfully, 6 cases discontinued glucocorticoid therapy among the rest, 6 cases continued anti-tuberculosis + glucocorticoid replacement therapy, and 2 cases died. Conclusion: Early diagnosis and proper anti-tuberculosis treatment can improve the prognosis of patients with adrenal tuberculosis. Moreover, screening and educating Tibetan people regarding the potential risk and adversities of adrenal tuberculosis is crucial for eradicating the disease.

Abstract Background A majority (>70%) of Q fever patients in South Korea do not have a history of animal contact. Therefore, unconscious environmental exposure is suspected. The aim of this study was to investigate exposure of Q fever patients to environmental contamination and animal shedding. Methods Two goat farmers were enrolled. One was diagnosed with Q fever 3 years ago (Farm 1). Among 20 goats on Farm 1, five were tested randomly and found to be Q fever PCR‐positive. Three of the five were Q fever ELISA‐positive. Two of five environmental samples taken in 2015 were PCR‐positive. In 2018, 17 of 18 environmental samples were PCR‐positive. On Farm 2, 54 of the 77 goats were PCR‐positive, and 63 were ELISA‐positive. Twelve of 14 environmental samples were PCR‐positive. Repeat administration of oxytetracycline to goats led to a gradual reduction in PCR‐positive tests over a 5‐month period. However, PCR‐positivity of the farm environment persisted for 5 months. Conclusion The environment on farms owned by Q fever patients was contaminated extensively and persistently, even after antibiotic treatment of goats and environmental decontamination. Undetected environmental contamination can be a major source of sporadic Q fever infection in South Korea.

Mastitis, inflammation of the mammary gland, is the most prevalent disease in dairy cattle that has a potential impact on profitability and animal welfare. Specifically designed multi-omics studies can be used to prioritize candidate genes and identify biomarkers and the molecular mechanisms underlying mastitis in dairy cattle. Hence, the present study aimed to explore the genetic basis of bovine mastitis by integrating microarray and RNA-Seq data containing healthy and mastitic samples in comparative transcriptome analysis with the results of published genome-wide association studies (GWAS) using a literature mining approach. The integration of different information sources resulted in the identification of 33 common and relevant genes associated with bovine mastitis. Among these, seven genes—CXCR1, HCK, IL1RN, MMP9, S100A9, GRO1, and SOCS3—were identified as the hub genes (highly connected genes) for mastitis susceptibility and resistance, and were subjected to protein-protein interaction (PPI) network and gene regulatory network construction. Gene ontology annotation and enrichment analysis revealed 23, 7, and 4 GO terms related to mastitis in the biological process, molecular function, and cellular component categories, respectively. Moreover, the main metabolic-signalling pathways responsible for the regulation of immune or inflammatory responses were significantly enriched in cytokine–cytokine-receptor interaction, the IL-17 signaling pathway, viral protein interaction with cytokines and cytokine receptors, and the chemokine signaling pathway. Consequently, the identification of these genes, pathways, and their respective functions could contribute to a better understanding of the genetics and mechanisms regulating mastitis and can be considered a starting point for future studies on bovine mastitis.

Abstract Background Sarcopenia is a significant indicator of the severity of non‐alcoholic fatty liver disease. We investigated whether sarcopenia could identify subgroups with different risk of liver fibrosis and atherosclerotic cardiovascular disease (ASCVD) among subjects with metabolic dysfunction‐associated fatty liver disease (MAFLD). Methods Subjects from the Korea National Health and Nutrition Examination Survey 2008–2011 were selected (n = 8361). Sarcopenia was defined using the sarcopenia index. Hepatic steatosis was defined as a fatty liver index ≥30. Significant liver fibrosis was defined as a fibrosis‐4 index (FIB‐4) ≥2.67 or the highest quartile of non‐alcoholic fatty liver disease fibrosis score (NFS). High probability of ASCVD was defined as ASCVD risk score >10%. Results The mean age was 48.5 ± 15.6 years, and 42.6% of subjects were male. The prevalence of MAFLD was 37.3% (n = 3116 of 8361), and the proportion of sarcopenic subjects was 9.9% among those with MAFLD. After adjusting for confounders, the risk of significant liver fibrosis significantly increased from non‐sarcopenic subjects with MAFLD [odds ratio (OR) = 1.57 by FIB‐4 and 2.13 by NFS] to sarcopenic subjects with MAFLD (OR = 4.51 by FIB‐4 and 5.72 by NFS), compared with subjects without MAFLD (all P

Although the individual consumption of medicinal mushrooms, including Phellinus linteus (PL), Ganoderma lucidum (GL), and Inonotus obliquus (IO), is known to be neuroprotective, the associated mechanisms underlying their therapeutic synergism on focal cerebral ischemia (fCI) have yet to be elucidated. This study aimed to demonstrate the neuroprotective effects of mixed mushroom mycelia (MMM) against experimental fCI. The water-fractions, ethanolic-fractions, and ethyl acetate-fractions of the MMM (PL, GL, and IO) grown in a barley medium using solid-state fermentation techniques were prepared and their protective effects against glutamate-induced excitotoxicity were compared in PC-12 cells. After the identification of the water extracts of MMM (wMMM) as the most suitable form, which possessed the lowest toxicity and highest efficacy, further analyses for evaluating the anti-apoptotic effects of wMMM, including Hoechst 33258-based nuclear staining, fluorescence-activated cell sorting, and reactive oxygen species (ROS) detection assays, were performed. Rats were subjected to a 90 min middle cerebral artery occlusion and reperfusion, after which a wMMM treatment resulted in significant dose-dependent improvements across a number of parameters. Furthermore, measurements of intracellular ROS and levels of antioxidant enzymes revealed a wMMM-mediated ROS attenuation and antioxidant enzyme upregulation. We suggest that wMMM is neuroprotective against fCI through its anti-apoptotic and anti-oxidative effects.

Abstract We investigated the association between body weight variability and the risks of cardiovascular disease and mortality in patients with nonalcoholic fatty liver disease (NAFLD) using large-scale, nationwide cohort data. We included 726,736 individuals with NAFLD who underwent a health examination between 2009 and 2010. NAFLD was defined as a fatty liver index ≥ 60, after excluding significant alcohol intake, viral hepatitis, and liver cirrhosis. Body weight variability was assessed using four indices, including variability independent of the mean (VIM). During a median 8.1-year follow-up, we documented 11,358, 14,714, and 22,164 cases of myocardial infarction (MI), stroke, and all-cause mortality, respectively. Body weight variability was associated with an increased risk of MI, stroke, and mortality after adjusting for confounding variables. The hazard ratios (HRs) (95% confidence intervals) for the highest quartile, compared with the lowest quartile, of VIM for body weight were 1.15 (1.10–1.20), 1.22 (1.18–1.26), and 1.56 (1.53–1.62) for MI, stroke, and all-cause mortality, respectively. Body weight variability was associated with increased risks of MI, stroke, and all-cause mortality in NAFLD patients. Appropriate interventions to maintain a stable weight could positively affect health outcomes in NAFLD patients.

Objectives: The optimal treatment option for carbapenem-resistant Acinetobacter baumannii (CRAB) is still limited. This study investigated the efficacy of three or more antibiotic types and regimens for treatment of CRAB infection in high CRAB endemic areas. Methods: A multicentre retrospective study was conducted to evaluate the efficacy of treatment types and regimens of CRAB infections in 10 tertiary hospitals in the Republic of Korea. The outcomes comprised 7-day and 28-day mortality, and clinical and microbiological responses at 7 days, 28 days, and the end of treatment. Nephrotoxicity and hepatotoxicity were evaluated as drug adverse reactions. Results: A total of 282 patients were included in the study. Among the CRAB strains, the two most susceptible antibiotics were colistin (99.6%) and minocycline (80.4%). A combination of colistin and carbapenem significantly reduced 7-day mortality, and a sulbactam-containing regimen significantly reduced 28-day mortality. Colistin monotherapy was significantly associated with increased 7-day and 28-day mortality. A minocycline-containing regimen showed the best microbiological responses at 7 days, 28 days, and the end of treatment. Colistin and tigecycline were associated with increased nephrotoxicity and hepatotoxicity, respectively. Subgroup analysis of patients with pneumonia showed similar results to the overall CRAB infection. Conclusions: A combination of colistin and carbapenem and sulbactam-containing regimen may contribute improved mortality in CRAB infections. Colistin monotherapy should be considered cautiously in severe CRAB infections or CRAB pneumonia. A minocycline-containing regimen showed the best microbiological responses, and further studies may be needed to evaluate improved mortality.

To solve the problem on poor performance of crop growth model in simulating crop growth process under water stress, three schemes including improving evapotranspiration parameterization scheme with Penman-Monteith method, building dynamic crop coefficient (Kc) and considering simultaneously two above-mentioned solutions which are respectively named as the PM, CC and PMCC schemes are used to improve WOFOST model. Their effects on model performance in simulating maize drought stress process are evaluated based on experiments of different sowing dates on 20 April, 30 April and 10 May conducted in Jinzhou in the year with normal precipitation (2012) and the dry year (2015 and 2018). The results show that compared with the default model, PM scheme plays a role in increasing potential evapotranspiration and transpiration rate in 2012, while CC scheme decreases (increases) transpiration rate as Kc is larger (smaller) than the model default value 1, respectively. Three schemes hardly affect simulation accuracies of soil moisture in rooted zone, total above ground production, leaf area index (ILA) and yield. In 2015, PM scheme makes ILA, total above ground production yield and soil moisture dramatically smaller than those with the default model after the jointing stage of maize. It also increases (decreases) transpiration rate before (after) the whorl stage of maize. After improving the model with CC scheme, ILA, total above ground production, yield and soil moisture are slightly larger than those simulated by the default model after the whorl stage, and the simulated transpiration rates are smaller (larger) than those simulated by the default model before (after) the whorl stage of maize. Nevertheless, the above-mentioned variables simulated by the improved model with PMCC scheme range between those simulated by the model with PM and CC schemes, and ILA, total above ground production and yield are obviously closer to the observations. Specifically, the mean increments of simulation accuracies for all growth periods in three sowing dates are 6%, 21% and 3% for ILA and 8%, 8% and 14% for total above ground production, respectively. The simulation accuracies of yield for three sowing dates increase by 66%, 63% and 66%, respectively. In 2018, the simulation accuracies of total above ground production and yield for the sowing dates on 20 April and 30 April are obviously improved by PMCC scheme, and increase by 5%, 1% in total above ground production as well as 32%, 5% in yield. Therefore, the model performance with PMCC scheme in simulating maize growth is significantly improved under water stress.

Objective The objective of this study was to characterize the number of loci affecting growth traits and the distribution of single nucleotide polymorphism (SNP) effects on growth traits, and to understand the genetic architecture for growth traits in Hanwoo (Korean cattle) using genome-wide association study (GWAS), genomic partitioning, and hierarchical Bayesian mixture models. Methods GWAS: A single-marker regression-based mixed model was used to test the association between SNPs and causal variants. A genotype relationship matrix was fitted as a random effect in this linear mixed model to correct the genetic structure of a sire family. Genomic restricted maximum likelihood and BayesR: A priori information included setting the fixed additive genetic variance to a pre-specified value; the first mixture component was set to zero, the second to 0.0001 × σ g 2, the third 0.001 × σ g 2, and the fourth to 0.01 × σ g 2. BayesR fixed a priori information was not more than 1% of the genetic variance for each of the SNPs affecting the mixed distribution. Results The GWAS revealed common genomic regions of 2 Mb on bovine chromosome 14 (BTA14) and 3 had a moderate effect that may contain causal variants for body weight at 6, 12, 18, and 24 months. This genomic region explained approximately 10% of the variance against total additive genetic variance and body weight heritability at 12, 18, and 24 months. BayesR identified the exact genomic region containing causal SNPs on BTA14, 3, and 22. However, the genetic variance explained by each chromosome or SNP was estimated to be very small compared to the total additive genetic variance. Causal SNPs for growth trait on BTA14 explained only 0.04% to 0.5% of the genetic variance Conclusion Segregating mutations have a moderate effect on BTA14, 3, and 19; many other loci with small effects on growth traits at different ages were also identified.

Objective Genomic selection (GS) is becoming popular in animals’ genetic development. We, therefore, investigated the single-step genomic best linear unbiased prediction (ssGBLUP) as tool for GS, and compared its efficacy with the traditional pedigree BLUP (pedBLUP) method. Methods A total of 9,952 males born between 1997 and 2018 under Hanwoo proven-bull selection program was studied. We analyzed body weight at 12 months and carcass weight (kg), backfat thickness, eye muscle area, and marbling score traits. About 7,387 bulls were genotyped using Illumina 50K BeadChip Arrays. Multiple-trait animal model analyses were performed using BLUPF90 software programs. Breeding value accuracy was calculated using two methods: i) Pearson’s correlation of genomic estimated breeding value (GEBV) with EBV of all animals (rM1) and ii) correlation using inverse of coefficient matrix from the mixed-model equations (rM2). Then, we compared these accuracies by overall population, info-type (PHEN, phenotyped-only; GEN, genotyped-only; and PH+GEN, phenotyped and genotyped), and bull-types (YBULL, young male calves; CBULL, young candidate bulls; and PBULL, proven bulls). Results The rM1 estimates in the study were between 0.90 and 0.96 among five traits. The rM1 estimates varied slightly by population and info-type, but noticeably by bull-type for traits. Generally average rM2 estimates were much smaller than rM1 (pedBLUP, 0.40 to 0.44; ssGBLUP, 0.41 to 0.45) at population level. However, rM2 from both BLUP models varied noticeably across info-types and bull-types. The ssGBLUP estimates of rM2 in PHEN, GEN, and PH+ GEN ranged between 0.51 and 0.63, 0.66 and 0.70, and 0.68 and 0.73, respectively. In YBULL, CBULL, and PBULL, the rM2 estimates ranged between 0.54 and 0.57, 0.55 and 0.62, and 0.70 and 0.74, respectively. The pedBLUP based rM2 estimates were also relatively lower than ssGBLUP estimates. At the population level, we found an increase in accuracy by 2.0% to 4.5% among traits. Traits in PHEN were least influenced by ssGBLUP (0% to 2.0%), whereas the highest positive changes were in GEN (8.1% to 10.7%). PH+GEN also showed 6.5% to 8.5% increase in accuracy by ssGBLUP. However, the highest improvements were found in bull-types (YBULL, 21% to 35.7%; CBULL, 3.3% to 9.3%; PBULL, 2.8% to 6.1%). Conclusion A noticeable improvement by ssGBLUP was observed in this study. Findings of differential responses to ssGBLUP by various bulls could assist in better selection decision making as well. We, therefore, suggest that ssGBLUP could be used for GS in Hanwoo proven-bull evaluation program.

Objective The purpose of this study was i) to identify the characteristics of carcass traits in Chikso by gender, region, age at slaughter, and coat color using the carcass data collected from the nationwide pedigree information and coat color investigation, and ii) to estimate genetic parameters for breed improvement. Methods A linear model was used to analyze the environmental effects on the carcass traits and to estimate genetic parameters. Analysis of variance was performed using TYPE III sum of squares for the unbalanced data provided by the general linear model procedure. Variance components for genetic parameters was estimated using REMLF90 of the BLUPF90 family programs. Results Phenotypic performance of carcass weight (CW), eye muscle area (EMA), and backfat thickness (BF) in Chikso were lower than those of Hanwoo. This is a natural outcome because Hanwoo have undergone significant efforts for improvement at the national level, a phenomenon not observed in Chikso. Another factor influencing the above outcome was the smaller population size of Chikso compared to that of Hanwoo’s. The heritabilities of CW, EMA, BF, and marbling score in Chikso were estimated as 0.50, 0.37, 0.35, and 0.53, respectively, which were was higher than those of Hanwoo. Conclusion Based on the genetic parameters that were estimated in this study, it is expected that the carcass traits will improve when the livestock research institutes at each province conduct small-scale performance tests and the semen is provided to farmers after selecting proven bulls using the state-of-art selection technique such as genomic selection.

Genetic and nutritional factors contribute to the development of non-alcoholic fatty liver disease (NAFLD); however, gene–diet interactions in NAFLD development are poorly understood. In this case–control study, a large dataset from the Korean Genome and Epidemiology Study cohort (n = 72,299) comprising genomic data, medical records, social history, and dietary data was used. We investigated the interactions between the PNPLA3 rs738409 genotype and nutritional factors and their possible effect on the risk of NAFLD development in 2950 patients with NAFLD and 12,907 controls. In the PNPLA3 risk allele group, high protein, fat, sodium, phosphorus, niacin, and vitamin B6 intakes were associated with a decreased risk of NAFLD. In the non-risk allele group, only high fat intake was associated with a decreased risk of NAFLD. Among these nutrients, high sodium intake had a significant protective interaction with the PNPLA3 genotype against NAFLD (p = 0.002). Among salty foods, only kimchi had a significant protective effect against the PNPLA3 genotype (p = 0.012). Thus, the PNPLA3 genotype is differentially associated with nutritional factors. In particular, it interacts with kimchi, a fermented vegetable dish. Therefore, fermented vegetables may serve as a tailored therapeutic food for people with the PNPLA3 risk allele.

The importance of meat and carcass quality is growing in beef cattle production to meet both producer and consumer demands. Primal cut yields, which reflect the body compositions of carcass, could determine the carcass grade and, consequently, command premium prices. Despite its importance, there have been few genome-wide association studies on these traits. This study aimed to identify genomic regions and putative candidate genes related to 10 primal cut traits, including tenderloin, sirloin, striploin, chuck, brisket, top round, bottom round, shank, flank, and rib in Hanwoo cattle using a single-step Bayesian regression (ssBR) approach. After genomic data quality control, 43,987 SNPs from 3,745 genotyped animals were available, of which 3,467 had phenotypic records for the analyzed traits. A total of 16 significant genomic regions (1-Mb window) were identified, of which five large-effect quantitative trait loci (QTLs) located on chromosomes 6 at 38–39 Mb, 11 at 21–22 Mb, 14 at 6–7 Mb and 26–27 Mb, and 19 at 26–27 Mb were associated with more than one trait, while the remaining 11 QTLs were trait-specific. These significant regions were harbored by 154 genes, among which TOX, FAM184B, SPP1, IBSP, PKD2, SDCBP, PIGY, LCORL, NCAPG, and ABCG2 were noteworthy. Enrichment analysis revealed biological processes and functional terms involved in growth and lipid metabolism, such as growth (GO:0040007), muscle structure development (GO:0061061), skeletal system development (GO:0001501), animal organ development (GO:0048513), lipid metabolic process (GO:0006629), response to lipid (GO:0033993), metabolic pathways (bta01100), focal adhesion (bta04510), ECM–receptor interaction (bta04512), fat digestion and absorption (bta04975), and Rap1 signaling pathway (bta04015) being the most significant for the carcass primal cut traits. Thus, identification of quantitative trait loci regions and plausible candidate genes will aid in a better understanding of the genetic and biological mechanisms regulating carcass primal cut yields.

Abstract Background The upper‐airway microbiota may be associated with the pathogenesis of asthma and useful for predicting acute exacerbation. However, the relationship between the lower‐airway microbiota and acute exacerbation in children with asthma is not well understood. We evaluated the characteristics of the airway microbiome using induced sputum from children with asthma exacerbation and compared the microbiota‐related differences of inflammatory cytokines with those in children with asthma. Methods We analysed the microbiome using induced sputum during acute exacerbation of asthma in children. We identified microbial candidates that were prominent in children with asthma exacerbation and compared them with those in children with stable asthma using various analytical methods. The microbial candidates were analysed to determine their association with inflammatory cytokines. We also developed a predictive functional profile using PICRUSt. Results A total of 95 children with allergic sensitisation including 22 with asthma exacerbation, 67 with stable asthma, and 6 controls were evaluated. We selected 26 microbial candidates whose abundances were significantly increased, decreased, or correlated during acute exacerbation in children with asthma. Among the microbial candidates, Campylobacter, Capnocytophaga, Haemophilus, and Porphyromonas were associated with inflammatory cytokines including macrophage inflammatory protein (MIP)‐1β, programmed death‐ligand 1, and granzyme B. Both Campylobacter and MIP‐1β levels were correlated with sputum eosinophils. Increased lipopolysaccharide biosynthesis and decreased glycan degradation were observed in children with asthma exacerbation. Conclusion Gram‐negative microbes in the lower airway were related to acute exacerbation in children with asthma. These microbes and associated cytokines may play a role in exacerbating asthma in children.

Rare sugars are regarded as functional biological materials due to their potential applications as low-calorie sweeteners, antioxidants, nucleoside analogs, and immunosuppressants. D-Allose is a rare sugar that has attracted substantial attention in recent years, owing to its pharmaceutical activities, but it is still not widely available. To address this limitation, we continuously produced D-allose from D-allulose using a packed bed reactor with commercial glucose isomerase (Sweetzyme IT). The optimal conditions for D-allose production were determined to be pH 8.0 and 60°C, with 500 g/L D-allulose as a substrate at a dilution rate of 0.24/h. Using these optimum conditions, the commercial glucose isomerase produced an average of 150 g/L D-allose over 20 days, with a productivity of 36 g/L/h and a conversion yield of 30%. This is the first report of the successful continuous production of D-allose from D-allulose by commercial glucose isomerase using a packed bed reactor, which can potentially provide a continuous production system for industrial applications of D-allose.

Background/Aims Antiviral therapy (AVT) reduces the risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B (CHB). This multicenter retrospective study investigated the effects of AVT and hepatitis B virus (HBV)-related factors on the risk of HCC development in a cohort with heterogeneous HBV status. Methods : A total of 1,843 patients with CHB from two institutions were included in this study. Ultrasound and laboratory tests, including the α-fetoprotein test, were conducted regularly to detect HCC development. Results : The mean age of our study population (1,063 men and 780 women) was 49.4 years. Cirrhosis was identified in 617 patients (33.5%). During follow-up (median, 42.5 months), 81 patients developed HCC (1.39% per person-year). A total of 645 patients (35.0%) received ongoing AVT at enrollment. Ongoing AVT was not significantly associated with the risk of HCC development (all p>0.05). HBV-related variables (HBV DNA level, hepatitis B e antigen status, and alanine aminotransferase level) were also not significantly associated with the risk of HCC development (all p>0.05). In contrast, cirrhosis was significantly associated with the risk of HCC development, regardless of adjustment (adjusted hazard ratio=4.098 to 7.020; all p

Background/Aims Nonalcoholic fatty liver disease (NAFLD) is becoming a worldwide epidemic, and is frequently found in patients with chronic hepatitis B (CHB). We investigated the impact of histologically proven hepatic steatosis on the risk for hepatocellular carcinoma (HCC) in CHB patients without excessive alcohol intake. Methods Consecutive CHB patients who underwent liver biopsy from January 2007 to December 2015 were included. The association between hepatic steatosis (≥ 5%) and subsequent HCC risk was analyzed. Inverse probability weighting (IPW) using the propensity score was applied to adjust for differences in patient characteristics, including metabolic factors. Results Fatty liver was histologically proven in 70 patients (21.8%) among a total of 321 patients. During the median (interquartile range) follow-up of 5.3 (2.9–8.3) years, 17 of 321 patients (5.3%) developed HCC: 8 of 70 patients (11.4%) with fatty liver and 9 of 251 patients (3.6%) without fatty liver. The five-year cumulative incidences of HCC among patients without and with fatty liver were 1.9% and 8.2%, respectively (P=0.004). Coexisting fatty liver was associated with a higher risk for HCC (adjusted hazards ratio [HR], 3.005; 95% confidence interval [CI], 1.122–8.051; P=0.03). After balancing with IPW, HCC incidences were not significantly different between the groups (P=0.19), and the association between fatty liver and HCC was not significant (adjusted HR, 1.709; 95% CI, 0.404–7.228; P=0.47). Conclusions Superimposed NAFLD was associated with a higher HCC risk in CHB patients. However, the association between steatosis per se and HCC risk was not evident after adjustment for metabolic factors.

This study was carried out to estimate the variance components, heritability, and genetic correlations between the carcass traits and primal cut yields in Hanwoo cattle. Carcass traits comprising 5622 records included back fat thickness (BFT), carcass weight (CW), eye muscle area (EMA), and marbling score (MS). The 10 primal cut yields from 3467 Hanwoo steers included the tenderloin (TLN), sirloin (SLN), striploin (STLN), chuck (CHK), brisket (BSK), top round (TRD), bottom round (BRD), rib (RB), shank (SK), and flank (FK). In addition, three composite traits were formed by combining primal cut yields as novel traits according to consumer preferences and market price: high-value cuts (HVC), medium-value cuts (MVC), and low-value cuts (LVC). Heritability estimates for the interest of traits were moderate to high, ranging from 0.21 ± 0.04 for CHK to 0.59 ± 0.05 for MS. Except genetic correlations between RB and other primal cut traits, favorable and moderate to high correlations were observed among the yields of primal cut that ranged from 0.38 ± 0.14 (CHK and FK) to 0.93 ± 0.01 (TRD and BRD). Moreover, the estimated genetic correlations of CW and EMA with primal cut yields and three composite traits were positive and moderate to strong, except for BFT, which was negative. These results indicate that genetic progress can be achieved for all traits, and selection to increase the yields of primal cuts can lead to considerable profitability in the Hanwoo beef industry.

Understanding animals’ genetic potential for carcass traits is the key to genetic improvements in any beef cattle. In this study, we investigated the genetic merits of carcass traits using Hanwoo males raised in a 30-month production system (PROD30). We achieved this using a dataset comprising 6092 Hanwoo males born between 2005 and 2017 and measures of four carcass traits (carcass weight, CWT; eye muscle area, EMA; backfat thickness, BFT; and marbling score, MS). Genetic parameters were estimated using a multiple-trait animal model through the AIREMLF90 program. According to the multiple-trait model, the h2 of CWT, EMA, BFT, and MS were 0.35 ± 0.04, 0.43 ± 0.05, 0.48 ± 0.05, and 0.56 ± 0.05, respectively. The strongest genetic correlation (rg) was obtained between CWT and EMA (0.49 ± 0.07), whereas it was negligible between CWT and BFT. EMA and MS were also moderately correlated, whereas there was a relatively low negative correlation between EMA and BFT (−0.26 ± 0.08). Our study revealed a consistent indirect genetic improvement in animals from 2005 onwards. Although Hanwoo improvement has mainly focused on males under a 24-month production cycle, we observed PROD30 males to have somewhat similar genetic potential. Our results provide useful insights into the genetic merits of PROD30 males for the first time, which may facilitate future studies on them and their integration into the Hanwoo National Evaluation for genomic selection.

The discovery of single nucleotide polymorphisms (SNP) and the subsequent genotyping of large numbers of animals have enabled large-scale analyses to begin to understand the biological processes that underpin variation in animal populations. In beef cattle, genome-wide association studies using genotype arrays have revealed many quantitative trait loci (QTL) for various production traits such as growth, efficiency and meat quality. Most studies regarding meat quality have focused on marbling, which is a key trait associated with meat eating quality. However, other important traits like meat color, texture and fat color have not commonly been studied. Developments in genome sequencing technologies provide new opportunities to identify regions associated with these traits more precisely. The objective of this study was to estimate variance components and identify significant variants underpinning variation in meat quality traits using imputed whole genome sequence data. Phenotypic and genomic data from 2,110 Hanwoo cattle were used. The estimated heritabilities for the studied traits were 0.01, 0.16, 0.31, and 0.49 for fat color, meat color, meat texture and marbling score, respectively. Marbling score and meat texture were highly correlated. The genome-wide association study revealed 107 significant SNPs located on 14 selected chromosomes (one QTL region per selected chromosome). Four QTL regions were identified on BTA2, 12, 16, and 24 for marbling score and two QTL regions were found for meat texture trait on BTA12 and 29. Similarly, three QTL regions were identified for meat color on BTA2, 14 and 24 and five QTL regions for fat color on BTA7, 10, 12, 16, and 21. Candidate genes were identified for all traits, and their potential influence on the given trait was discussed. The significant SNP will be an important inclusion into commercial genotyping arrays to select new breeding animals more accurately.

Exposure to high oxygen concentrations leads to generation of excessive reactive oxygen species, causing cellular injury and multiple organ dysfunctions and is associated with a high mortality rate. Clusterin (CLU) is a heterodimeric glycoprotein that mediates several intracellular signaling pathways, including cell death and inflammation. However, the role of CLU in the pathogenesis of hyperoxic acute lung injury (HALI) is unknown. Wild-type (WT) and CLU-deficient mice and cultured human airway epithelial cells were used. Changes in cell death- and inflammation-related molecules with or without hyperoxia exposure in cells and animals were determined. Hyperoxia induced an increase in CLU expression in mouse lungs and human airway epithelial cells. Mice lacking CLU had increased HALI and mortality rate compared with WT mice. In vitro, CLU-disrupted cells showed enhanced release of cytochrome c, Bax translocation, cell death and inflammatory cytokine expression. However, treatment with recombinant CLU attenuated hyperoxia-induced apoptosis. Moreover, the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed metabolic pathways, hematopoietic cell lineage, response to stress and localization and regulation of immune system that were differentially regulated between WT and CLU−/− mice. These results demonstrate that prolonged hyperoxia-induced lung injury is associated with CLU expression and that CLU replenishment may alleviate hyperoxia-induced cell death.

Adipose tissue in the loin muscle area of beef cattle as a marbling factor is directly associated with beef quality. To elucidate whether properties of proteins involved in depot specific adipose tissue were sex-dependent, we analyzed protein expression of intramuscular adipose tissue (IMAT) and omental adipose tissue (OMAT) from Hanwoo cows, steers, and bulls of Korean native beef cattle by liquid chromatography-tandem mass spectrometry (LC-MS/MS)–based proteomic analysis, quantitative polymerase chain reaction (PCR) and western blot analysis. Two different adipose depots (i.e. intramuscular and omental) were collected from cows (n = 7), steers (n = 7), or bulls (n = 7). LC-MS/MS revealed a total of 55 and 35 proteins in IMAT and OMAT, respectively. Of the 55 proteins identified, 44, 40, and 42 proteins were confirmed to be differentially expressed in IMAT of cows, steers, and bulls, respectively. In OMAT of cows, steers, and bulls, 33, 33, and 22 were confirmed to be differentially expressed, respectively. Tropomyosin (TPM) 1, TPM 2, and TPM3 were subjected to verification by quantitative PCR and western blot analysis in IMAT and OMAT of Hanwoo cows, steers, and bulls as key factors closely associated with muscle development. Both mRNA levels and protein levels of TPM1, TPM2, and TPM3 in IMAT were lower in bulls compared to in cows or steers suggesting that they were positively correlated with marbling score and quality grade. Our results may aid the regulation of marbling development and improvement of meat quality grades in beef cattle.

Multiple enchondromas are well described in the literature, however, the associated spectrum of MR imaging findings remains unclear. Secondary chondrosarcoma of the hand and feet associated with multiple enchondromas is extremely rare. Herein, we reported a case of multiple enchondromas of intramedullary, intracortical, and periosteal location with associated low-grade chondrosarcomas in the lower extremities on MR imaging in a 57-year-old woman.

Extensive studies with Arabidopsis thaliana suggested that calcineurin B-like (CBL) proteins constitute a unique family of calcium sensors in plants, which mediate a variety of abiotic stress responses. However, little is known about their function in most plants that do not have available genome sequences. In this study, we have developed a pair of universal primers that make it possible to isolate CBL1-like genes from various plants without sequence information. Using these primers, we successfully cloned a full-length cDNA of CBL1-like gene in Sedirea japonica (SjCBL1). Bimolecular fluorescence complementation (BiFC) and pull-down assays demonstrated that like Arabidopsis CBL1 (AtCBL1), SjCBL1 can interacts physically with Arabidopsis CBL-interacting protein kinase 1 (AtCIPK1) at the plasma membrane of plant cells in a Ca2+-dependent manner. In addition, overexpression of SjCBL1 in the Arabidopsis cbl1 mutant resulted in not only rescuing the hypersensitive phenotype toward salt and osmotic stresses, but also substantially enhancing the tolerance to them. Taken together, these results strongly suggest that SjCBL1 is a functional ortholog of AtCBL1 in Sedirea japonica, which can play a critical role in response to salt and osmotic stresses. Therefore, it is clear that our findings should significantly contribute to broadening and deepening our understanding of the CBL1-mediated Ca2+ signaling networks in the plant kingdom.

In vitro biodegradation of Bombyx mori silk fibroin (SF) was studied using food-grade proteolytic enzymes to replace acid hydrolysis. Based on the residual protein quantity and yield of amino acids (AAs) after enzymatic hydrolysis, we evaluated the proteolytic enzyme process of SF. FoodPro and Alcalase that are classified as alkaline proteases are selected as two of the best candidate enzymes for hydrolysis of SF. The activity of these enzymes exhibits a broad range of pH (6.5 to 9.0) and temperature (50°C to 65°C). The single enzyme treatment of SF using FoodPro exhibited a hydrolytic efficiency of 20–25%, and >2 g/L AAs were released after reaction for 3 h. A 2-stage enzymatic treatment using a combination of FoodPro and Flavourzyme in a sequence for a reaction time of 6 h was developed to enhance the efficiency of the proteolytic process. The yield of AAs and residual protein quantity in the enzymatic hydrolysates obtained from FoodPro-treated regenerated SF in the 1st step was 2,040 ± 23.7 mg/L and 70.6%, respectively. The yield of AAs was > two-fold (4,519 ± 42.1 mg/L), whereas the residual protein quantity decreased to 55.1% after the Flavourzyme treatment (2nd step) compared to those of the single FoodPro treatment. In the mixed treatment by simultaneously using FoodPro and Flavourzyme, approximately 45% of SF was degraded and 4.5 g/L of AAs were released within 3 h of reaction time. The regenerated SF and its enzymatic hydrolysates were characterized by performing UV-visible spectra, gel electrophoresis, and size-exclusion chromatography analyses. In the 2-stage treatment using FoodPro initially and subsequently Flavourzyme, the aggregates and high molecular weight proteins of SF were dissociated and degraded into the low molecular weight proteins/peptides (10–15 kDa and 27 kDa). SF hydrolysates as functional food might be enzymatically produced using the commercial food-grade proteolytic enzymes.

Vertebral artery loop formation is an anatomic variation that possibly causes cervical nerve root compression, leading to cervical radiculopathy. A few cases of vertebral artery loop formation depicted with conventional sagittal magnetic resonance imaging (MRI) have been reported, but cases of vertebral artery loop formation depicted with oblique sagittal MRI have been less frequently reported. We present a case of vertebral artery loop formation depicted on oblique sagittal MRI.

Capsaicin is a major constituent of hot chili peppers that influences lipid metabolism in animals. In this study, we explored the effects of capsaicin on adipogenic differentiation of bovine bone marrow mesenchymal stem cells (BMSCs) in a dose- and time-dependent manner. The BMSCs were treated with various concentrations of capsaicin (0, 0.1, 1, 5, and 10 μM) for 2, 4, and 6 days. Capsaicin suppressed fat deposition significantly during adipogenic differentiation. Peroxisome proliferator-activated receptor gamma, cytosine-cytosine-adenosine-adenosine-thymidine/enhancer binding protein alpha, fatty acid binding protein 4, and stearoyl-CoA desaturase expression decreased after capsaicin treatment. We showed that the number of apoptotic cells increased in dose- and time-dependent manners. Furthermore, we found that capsaicin increased the expression levels of apoptotic genes, such as B-cell lymphoma 2-associated X protein and caspase 3. Overall, capsaicin inhibits fat deposition by triggering apoptosis.