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IL-10+ regulatory B (Breg) cells play a vital role in regulating the immune responses in experimental autoimmune encephalomyelitis, colitis, and contact hypersensitivity (CHS). Several stimulants such as lipopolysaccharide (LPS), CD40 ligand, and IL-21 spur the activation and maturation of IL-10+ Breg cells, while the epigenetic mechanism for the IL-10 expression remains largely unknown. It is well accepted that the histone acetylation/ deacetylation is an important mechanism that regulates the expression of IL-10. We found that entinostat, an HDAC inhibitor, stimulated the induction of IL-10+ Breg cells by LPS in vitro and the formation of IL-10+ Breg cells to suppress CHS in vivo. We further demonstrated that entinostat inhibited HDAC1 from binding to the proximal region of the IL-10 expression promoter in splenic B cells, followed by an increase in the binding of NF-κB p65, eventually enhancing the expression of IL-10 in Breg cells. [BMB Reports 2021; 54(10): 534-539].

BackgroundRecently, allogeneic natural killer (NK) cells have gained considerable attention as promising immunotherapeutic tools due to their unique biological functions and characteristics. Although many NK expansion strategies have been reported previously, a deeper understanding of cryopreserved allogeneic NK cells is needed for specific therapeutic approaches.MethodsWe isolated CD3−CD56+primary natural killer (pNK) cells from healthy donors and expanded them ex vivo using a GMP-compliant method without any feeder to generate large volumes of therapeutic pNK cells and cryopreserved stocks. After validation for high purity and activating phenotypes, we performed RNA sequencing of the expanded and cryopreserved pNK cells. The pNK cells were used against various cancer cell lines in 7-AAD/CFSE cytotoxicity assay. For in vivo efficacy study, NSG mice bearing subcutaneous cisplatin-resistant A2780cis xenografts were treated with our pNK cells or cisplatin. Antitumor efficacy was assessed by measuring tumor volume and weight.ResultsCompared to the pNK cells before expansion, pNK cells after expansion showed 2855 upregulated genes, including genes related to NK cell activation, cytotoxicity, chemokines, anti-apoptosis, and proliferation. Additionally, the pNK cells showed potent cytolytic activity against various cancer cell lines. Interestingly, our activated pNK cells showed a marked increase in NKp44 (1064-fold), CD40L (12,018-fold), and CCR5 (49-fold), and did not express the programmed cell death protein 1(PD-1). We also demonstrated the in vitro and in vivo efficacies of pNK cells against cisplatin-resistant A2780cis ovarian cancer cells having a high programmed death-ligand 1(PD-L1) and low HLA-C expression.ConclusionsTaken together, our study provides the first comprehensive genome wide analysis of ex vivo-expanded cryopreserved pNK cells. It also indicates the potential use of expanded and cryopreserved pNK cells as a highly promising immunotherapy for anti-cancer drug resistant patients.

Purpureocillium lilacinum is a saprophytic fungus with a ubiquitous environmental distribution, and it can be detected in soil samples and decaying materials worldwide. It has been reported as an emerging pathogen in both immunocompromised and immunocompetent patients, showing various cutaneous presentations. Herein, we report a case of a patient with a localized cutaneous P. lilacinum infection, which resembles the skin lesions of psoriasis. A 72-year-old female was presented with a peripherally spreading, well-demarcated, asymptomatic, scaly, erythematous patch on her forehead for several months. Histopathological examination showed pinkish septated fungal elements and mixed inflammatory and granulomatous infiltrates in the dermis. Furthermore, a fungal culture on potato dextrose agar showed gray, velvety colonies with light yellow background after being subcultured. Phialides with chains of oval conidia were observed on lactophenol cotton blue staining. The ITS region of rRNA gene sequence obtained from the colony was identical to that of Purpureocillium lilacinum. The lesion was resolved with oral itraconazole (200 mg/day) after four months of treatment.

Background Gonadotropin‐releasing hormone (GnRH) plays a pivotal role in regulating the reproductive endocrine system. Objective An immunocontraception vaccine aimed at inhibiting the functions of GnRH is tested as a potential tool for controlling animal populations. Methods We developed a recombinant immunocontraceptive vaccine composed of GnRH‐I and GnRH‐II (GnRH I+II), which was conjugated with Salmonella typhimurium flagellin. Forty‐eight BALB/c mice aged 4 weeks were divided into four groups (each group had n = 12): non‐vaccinated male (NVM), non‐vaccinated female (NVF), vaccinated male (VM), and vaccinated female (VF). Mice in the vaccinated groups were vaccinated twice by intramuscular injection at 0 and 2 weeks with 300 μg of the recombinant GnRH protein complex per mouse. Mice in the non‐vaccinated groups were injected with saline and served as the unimmunized controls. Twenty‐four pairs of male and female mice were mated for 10–12 weeks after initial immunization in four groups: 6 NVF × 6 NVM, 6 VF × 6 NVM, 6 NVF × 6 VM, and 6 VF × 6 VM. Results: An increase (p, We developed a new form of immunocontraceptive vaccine composed of GnRH‐I and ‐II complex conjugated with STF‐2. We provide the vaccine efficacies with higher anti‐GnRH antibodies in mice. The vaccine containing the GnRH‐I + II peptide linked to STF‐2 induced the suppression of fertility by inhibiting testicular and ovarian functions and reducing sex hormone levels in both male and female mice. In addition, the effects of fertility reduction were confirmed through mating experiments .

The emergence of antibiotic-resistant bacterial pathogens in the environment has been increasing, posing a threat to public health. Next-generation sequencing technology, which is both low cost and large scale, was used to identify antibiotic-resistance genes or toxin genes in these pathogens. Short-read sequencing cannot fully reconstruct bacterial chromosomes and plasmids carrying toxin genes and antibiotic-resistance genes because of their location on the insertion sequences or repeat regions. Third-generation sequencing generated long reads that could cover the repetitive and/or insertion sequences, allowing for complete chromosome and plasmid reconstruction. However, the optimal protocols for whole-genome sequencing of antibiotic-resistance pathogenic bacteria, from DNA extraction to genome assembly, are still being researched. To develop a pipeline of optimal methods for whole-genome sequencing of bacteria, we compared three commercial DNA extraction kits (column extraction, magnetic bead extraction, and precipitation extraction), two third-generation sequencing platforms (MinION and PacBio), and three assembly methods (flye, unicycler, and unicycler_hybrid). The assembly results were evaluated based on the number of contigs and the detection of anti-microbial-resistance genes. Magnetic bead extraction method generated longer N50 read lengths and greater read length distribution than the other two extraction methods. The Flye assembler in combination with magnetic bead extraction and MinION sequencing provided consistent successful plasmid assembly results and detected all antimicrobial-resistance gene in all datasets. DNA extraction, sequencing platform, and assembly methods can all have an impact on the results of bacterial whole-genome sequencing. Our findings could be a practical protocol for researchers who use third-generation sequencing to perform bacterial whole-genome sequencing by consistently resolving small plasmids carrying antibiotic-resistance genes.

Canine influenza virus (CIV) induces acute respiratory disease in dogs. In this study, we aimed to determine the signaling pathways leading to the induction of IFN-β in a canine respiratory epithelial cell line (i.e., KU-CBE) infected with the H3N2 subtype of CIV. Small interfering RNAs (siRNAs) specific to pattern recognition receptors (PRRs) and transcription factors were used to block the IFN-β-induction signals in H3N2 CIV-infected KU-CBE cells. Among the PRRs, only the TLR3 and RIG-I expression levels significantly (P < 0.001) increased in CIV-infected cells. Following transfection with siRNA specific to TLR3 (siTLR3) or RIG-I (siRIG-I), the mRNA expression levels of IFN-β significantly (P < 0.001) decreased, and the protein expression of IFN-β also decreased in infected cells. In addition, co-transfection with both siTLR3 and siRIG-I resulted in the significant reduction of IRF3 (P < 0.001) and IFN-β (P < 0.001) mRNA levels. Moreover, the protein concentration of IFN-β was significantly (P < 0.01) lower in cells co-transfected with both siTLR3 and siRIG-I than in cells transfected with either siTLR3 or siRIG-I alone. The antiviral protein MX1was only expressed in KU-CBE cells infected with CIV or treated with IFN-β or IFN-α. Thus, we speculate that the IFN-β further induces MX1 expression that might suppress CIV replication. These data indicate that TLR3 and RIG-I synergistically induce IFN-β expression via the activation of IRF3. The IFN-β produced further induces the production of MX1, which would suppress CIV replication in CIV-infected cells.

In June 2019, Angelica acutiloba plants showing virus-like symptoms such as chlorotic local lesion and mosaic on the leaves were found in a greenhouse in Nonsan, South Korea. To identify the causal virus, we collected 6 symptomatic A. acutiloba leaf samples and performed reverse transcription polymerase chain reaction (RT-PCR) analysis using specific detection primers for three reported viruses including tomato spotted wilt virus (TSWV). RT-PCR results showed that five symptomatic samples were positive for TSWV. Mechanical sap inoculation of one of the collected TSWV isolate (TSWV-NS-AG28) induced yellowing, chlorosis and mosaic symptoms in A. acutiloba and necrotic local lesions and mosaic in Solanaceae species. Phylogenetic analysis based on the complete genome sequences showed that TSWV-NS-AG28 had a maximum nucleotide identity with TSWV-NS-BB20 isolated from butterbur in Nonsan, South Korea. To our knowledge, this is the first report of TSWV infection in A. acutiloba.

The yellow-legged hornet, Vespa velutina nigrithorax (Hymenoptera: Vespidae), invaded South Korea in 2003 through Busan metropolitan city, which is located in the southeast region of the country. Previous studies aiming to trace the origin of V. velutina in Korea used a portion of mitochondrial (mt) COI and detected a single haplotype common to the site of origin. However, no subsequent study on invasive dynamics such as additional entry and/or another site of entry has been performed. In this study, segments of mt COI, CytB, and lrRNA were sequenced from 238 individuals collected in 11 Korean and two Japanese localities, but no variation in each gene was observed. Thus, we developed two intergenic spacer (IGS) sequences from the publicly available mt genome of V. velutina, which provided substantially increased variability (i.e., 19 haplotypes with 1.74% maximum sequence divergence in 1,129–1,146-bp-long concatenated sequences). Population genetic analyses using the concatenated sequences unexpectedly provided higher genetic diversity estimates in the northwest and southwest regions, both of which also harbor international cargo ports, than in the southeast region, in which Busan is located. Furthermore, this genetic result was roughly concordant with our questionnaire survey demonstrating that V. velutina was observed in apiaries located in the northwest and southwest regions up to 2012, when there was no reported prevalent distribution of the hornet beyond the southeast region. These results collectively suggest that the northwest and southwest regions of Korea are additional sites of V. velutina entry to the country, independent from the southeast region origin.

During the post-entry quarantine inspection of olive seedlings imported from the Netherlands, the olive psyllid, Euphyllura olivina (Costa, 1839), was accidentally intercepted in June 2020. This study reports the presence of the olive psyllid for the first time in the East Palaearctic region, South Korea. The damage inflicted by the insect through direct feeding, wax secretion, and abundant honeydew production results in the growth of sooty mold and may be of phytosanitary concern. Until now, the settlement of the psyllid in the Netherlands and South Korea has not been confirmed.

A new species of Eumerus from South Korea, Eumerus platycodon Choi and Hong sp. nov., is described. The new species discovered from roots of Platycodon grandiflorum (balloon flower) and Adenophora triphylla var. japonica belonging to the family Campanulaceae. The larvae burrow into the soil and pupate over a 10-day period. There are at least two generations per year. The diagnosis, description, and color photographs of the external structures, including the male genitalia, are provided to help identify this species accurately. The following characters distinguish it from the other species of the Northeast Asian species: 1) pilose eyes in both sexed; 2) different antennal basoflagellomere color in both sexes; and 3) orange-brown maculae on tergite 2. In addition to classical morphological characteristics, mitochondrial COI barcode sequences were generated for several specimens.

Background Umbilical cord-mesenchymal stem cell-conditioned medium (UC-MSC-CM) has emerged as a promising cell-free therapy. The aim of this study was to explore the therapeutic effects of UC-MSC-CM on insulin resistance in C2C12 cell. Methods Insulin resistance was induced by palmitate. Effects of UC-MSC-CM on insulin resistance were evaluated using glucose uptake, glucose transporter type 4 (GLUT4) translocation, the insulin-signaling pathway, and mitochondrial contents and functions in C2C12 cell. Results Glucose uptake was improved by UC-MSC-CM. UC-MSC-CM treatment increased only in membranous GLUT4 expression, not in cytosolic GLUT4 expression. It restored the insulin-signaling pathway in insulin receptor substrate 1 and protein kinase B. Mitochondrial contents evaluated by mitochondrial transcription factor A, mitochondrial DNA copy number, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were increased by UC-MSC-CM. In addition, UC-MSC-CM significantly decreased mitochondrial reactive oxygen species and increased fatty acid oxidation and mitochondrial membrane potential. There was no improvement in adenosine triphosphate (ATP) contents, but ATP synthesis was improved by UC-MSC-CM. Cytokine and active factor analysis of UC-MSC-CM showed that it contained many regulators inhibiting insulin resistance. Conclusion UC-MSC-CM improves insulin resistance with multiple mechanisms in C2C12 cell.

The detection of Mycobacterium bovis (M. bovis) in environmental samples with precision is imperative to control bovine tuberculosis (bTB) infections at the herd level, as residual M. bovis remains one of the major causes of recurring infections. In this study, a nested PCR method for the detection of M. bovis in environmental samples was applied to identify potential environmental reservoirs of the bacterium. A set of 200 environmental samples (167 fecal samples and 33 water samples) from 39 herds with a history of bTB outbreak was analyzed using a nested PCR method to detect residual M. bovis. Amplicon libraries of the IS6110 target gene fragment were amplified from M. bovis DNA using two established primer sets. A positive nested PCR result was observed in 69.5% of fecal samples and 66.7% of water samples, thus showing that residual M. bovis was present in the environmental samples of bTB-positive herds in a high proportion. This study is the first to demonstrate high levels of M. bovis DNA in environmental samples and to show that environmental reservoirs of this pathogen contribute to recurring outbreaks of bTB. Environmental monitoring of herds in which bTB outbreaks have occurred with high sensitivity and specificity is expected to help prevent the recurrence of potential bTB disease and improve the herd environment.

TFEB, a key regulator of lysosomal biogenesis and autophagy, is induced not only by nutritional deficiency but also by organelle stress. Here, we find that Tfeb and its downstream genes are upregulated together with lipofuscin accumulation in adipose tissue macrophages (ATMs) of obese mice or humans, suggestive of obesity-associated lysosomal dysfunction/stress in ATMs. Macrophage-specific TFEB-overexpressing mice display complete abrogation of diet-induced obesity, adipose tissue inflammation and insulin resistance, which is independent of autophagy, but dependent on TFEB-induced GDF15 expression. Palmitic acid induces Gdf15 expression through lysosomal Ca2+-mediated TFEB nuclear translocation in response to lysosomal stress. In contrast, mice fed a high-fat diet with macrophage-specific Tfeb deletion show aggravated adipose tissue inflammation and insulin resistance, accompanied by reduced GDF15 level. Finally, we observe activation of TFEB–GDF15 in ATMs of obese humans as a consequence of lysosomal stress. These findings highlight the importance of the TFEB–GDF15 axis as a lysosomal stress response in obesity or metabolic syndrome and as a promising therapeutic target for treatment of these conditions. Kim et al. reveal that TFEB expression is protective in the setting of diet-induced obesity by activating the expression of GDF15 in adipose tissue macrophages in mice and humans.

In September 2017, vein clearing and yellowing symptoms resembling those caused by viruses were observed on leaves of Malva verticillata in Chungnam, Korea. Nucleic acids were extracted from leaves of five symptomatic plants and tested by reverse transcription polymerase chain reaction using four virus specific primer pairs including malva vein clearing virus (MVCV). Amplicons of the expected size (600 bp) were obtained from total RNA of all samples using the MVCV-specific primers. To confirm the presence of MVCV in symptomatic plants, the DNA fragments from three samples were purified, and directly sequenced. BLAST analysis revealed that it shared the highest nucleotide identity (99%) with a MVCV isolate from tomato (Mexico). The virus isolates obtained from the third re-inoculated Chenopodium was designated as Cm1-5. Tissue from Cm1, Cm3, and Cm5 isolates was mechanically sap inoculated into 23 indicator plants. Cm3 isolate induced chlorotic local and mosaic symptoms in Althaea rosea. Phylogenetic analysis based on coat protein gene of 19 MVCV isolates from 6 different countries and plant species, did not correlated with either the geographical origin of the isolates, or pathogenicity. To our knowledge, this study first reports the natural occurrence of MVCV on M. verticillata in Korea and characterization of three Korean isolates of MVCV.

Morphological (cyst shape, color, and sizes [length (L), maximum width (W), volume and “a” (L/W)]), structural (vulvar cone slope angle [VCSA], surface wrinkle [VCSW], cyst wall thickness, composition, and texture) and biological characteristics (fecundity, hatching, and emergence [number of second-stage juveniles (J2) from a cyst]) in preceding Heterodera glycines (Hg), currently- recorded H. sojae (Hs) and H. trifolii (Ht) were examined by microscopy. Cysts were lemon-shaped, indicating the genus is Heterodera except for Hs that formed frequently globular cysts with significantly flatter VCSA (102.2°) with smooth VCSW than Hg (50.6°) and Ht (82.0°), but not genus Globodera because of the presence of vulvar cone in Hs. Ht was significantly larger in all morphological characteristics than Hg and Hs, suggesting Ht may be diagnosed differentially by cyst sizes and also host plant preferences. Hs showed smaller “a” value with more globular shape and stronger structures with more thickened and strengthened collagen-like texture of cyst wall than Hg and Ht. This suggests Hs may be diagnosed differently by structural characteristics from the others, especially Hg with similar cyst sizes. There were no significant differences in emergence (inoculum potential) among cyst nematodes due to the offset of fecundity and hatching rate; however, the inoculum potential of Hs may be not so persistent as Hg and Ht in fields because of its lower fecundity and higher hatching rate (causing rapid inoculum loss) than the others. These characteristics of cysts provide information useful for simple and differential diagnoses and reliable management of cyst nematodes.

Background Sepsis is associated with high mortality, and the related innate immune system activation and diagnostic factors are not fully understood. This study aimed to statistically analyse the clinical value of full-length tryptophanyl-tRNA synthetase (WRS) induced through inflammatory stimuli in the detection of sepsis and mortality prediction in critically ill patients. Method In this retrospective analysis, we prospectively collected blood samples from patients in the medical intensive care unit (ICU) at Yonsei University College of Medicine, from March 2015 to June 2018. Sepsis detection and mortality prediction using WRS levels were compared to that with procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6) levels, and with Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, using area under the receiver operating characteristic curve (AUROC) and Cox proportional-hazards and Kaplan-Meier survival analyses.Results We enrolled 241 study patients, of whom 190 (78.8%) had been diagnosed with sepsis on ICU admission. The AUROCs for sepsis discrimination with WRS, PCT, CRP, and IL-6 levels, and SOFA and APACHE II scores were 0.864, 0.727, 0.625, 0.651, 0.840, and 0.754, respectively. The prediction of 28-day mortality in patients with sepsis using WRS levels was possible and non-inferior to that with the SOFA score (WRS vs. SOFA, AUROC 0.687 vs. 0.711; AUROC difference, 0.024; P = 0.650). Conclusions WRS secreted early in sepsis may be useful not only for early detection of sepsis but also for mortality prediction in critically ill patients.

Abeliophyllum distichum Nakai is a Korean endemic plant of the Oleaceae family that contains acteoside, a glycosylated caffeic acid, with neuroprotective, anti‑inflammatory and antibacterial properties. Previous studies, involving Accelerated Chromatographic Isolation, a high‑performance liquid chromatography‑photodiode array detector and a liquid chromatograph‑mass selective detector, isolated and identified acteoside in A. distichum (AAD) and documented its antioxidant and anti‑inflammatory activities. The aim of the present study was to determine whether AAD could protect from DNA damage by reducing oxidative stress. AAD treatment protected plasmid DNA against damage to DNA double‑strands induced by reactive oxygen species (ROS) and decreased the levels of phosphorylated p53 and γ‑H2AX in ROS‑treated NIH 3T3 cells. These findings suggested that AAD could reduce ROS‑mediated cellular damage and may represent an effective, natural antioxidant with the ability to protect genetic material.

Polygalacturonase (PG) activity in plants can serve as an important index for plant disease. However, the conventional method to detect PG activity is a complex process and requires a skilled technician and expensive analytical equipment. In this study, a paper-based colorimetric sensor was developed based on the principle of the ruthenium red (RR) dye method for easy and simple measurement of PG activity. The proposed paper-based sensor has a three-layer structure for detection of PG activity in samples. The sensor sensitivity was enhanced by optimizing the pH of the sodium acetate buffer used in polygalacturonic acid (PGA)-RR complex formation and the reaction temperature for PG and the PGA-RR complex. Further, for quantitative analysis of PG activity, Delta RGB analysis was conducted to detect color changes in the sensing window of the sensor. Results presented that the linear measurement range of the paper sensor was 0.02-0.1 unit with the limit of detection of 0.02 unit, which showed a similar detection range, but a lower detection limit, compared to the spectrophotometry. Furthermore, PG activity based on culture condition was measured using samples from Sclerotium cepivorum to verify the potential application of the developed paper-based sensor in the field. The measured activity showed no statistically significant difference from the values obtained from the spectrophotometry at 95% confidence level. Therefore, the paper-based colorimetric sensor can be used to predict plant diseases in Allium crops during the stage of pathogen invasion, potentially contributing to the improvement of crop production.

Korean greenhouse strawberries are mostly cultivated from October to May, which includes the cold winter season. During this time, the population size of the spotted-wing drosophila (SWD), Drosophila suzukii Matsumura (Diptera: Drosophilidae), is expected to decrease in the wild, and is also expected to decrease inside the greenhouses, as long as SWD are not already present inside. Field surveys of SWD have been extensively carried out for field-grown agricultural fruits, but no study has been conducted for greenhouse fruits, such as strawberries. In this study, SWD capture patterns were examined inside and outside of the greenhouse blocks, and in the nearby woodlands in a southwestern locality of Korea using selected traps and attractants for nearly 19 months—in addition to several greenhouse blocks—during the strawberry cultivating periods. The highest capture period was observed from October to mid-December in woodlands, whereas capture number subsequently and sharply decreased up to mid-April, resulting in mostly zero-captures or low captures (≤10). During this period, a zero-capture period was observed inside the greenhouse that lasted for nearly three months (late December to late February). An incubation of the fallen strawberries supported the results of trap capture from inside the greenhouses. Taken together, the occurrence of SWD in the strawberry greenhouses is likely to be highly dependent on that of the nearby woodlands. Thus, a sharp winter drop and the subsequent zero- or low-capture periods in the woodland areas were likely responsible for the observed zero-capture periods inside the greenhouses.

Skeletal muscle is a major organ for glucose disposal and thermogenesis. While hepatic fructose-1,6-bisphosphatase is well known as a key enzyme for gluconeogenesis, the role of muscle fructose-1,6-bisphosphatase 2 (Fbp2) in glucose disposal and thermogenesis is unknown. Here, using Fbp2 knockout (KO) mice, we assessed the physiological role of Fbp2 in energy and glucose metabolism and thermogenesis. In vivo assessments of energy metabolism, glucose metabolism, and thermogenesis were performed by indirect calorimetry, hyperinsulinemic-euglycemic clamp, and cold challenge studies, respectively. Under both feeding and fasting conditions, Fbp2 KO mice showed similar phenotypes regarding energy and glucose metabolism compared to wild-type (WT) mice. However, Fbp2 KO mice were severely intolerant to cold challenge under fasting conditions. Mechanistically, the cold-induced intramuscular conversion of lactate to glycogen (glyconeogenesis) is completely abolished in the KO muscle, which leads to a lack of glycogen source for thermogenesis in Fbp2 KO mice. The cold-intolerant phenotype of KO mice disappeared after feeding, and the KO mice were equally as cold tolerant as the WT mice and survived during the cold challenge for three weeks. Taken together, these data demonstrate that Fbp2 is essential for muscle thermogenesis by replenishing the intramuscular glycogen pool through glyconeogenesis when the exogenous glucose source is limited. These data imply the physiological importance of Fbp2 in thermal homeostasis and suggest a potential novel therapy targeted to increase glycogen replenishment upon cold stress., Body temperature: Enzyme critical to heat production in muscle When simple sugars in the diet are scarce, skeletal muscle can still generate heat under cold conditions thanks to an enzyme that converts a metabolic byproduct into complex carbohydrates. A team led by Hui-Young Lee and Cheol Soo Choi from Gachon University’s Lee Gil Ya Cancer and Diabetes Institute in Incheon, South Korea, showed that, under fasting conditions, mice lacking a muscle form of enzyme called fructose-1,6-bisphosphatase 2 (Fbp2) could not respond to cold exposure by the usual process of converting lactate, which builds up in muscles during intense activity, into glycogen, a type of complex sugar involved in heat production not related to shivering. After a meal, however, the same mice could adapt to extreme cold without any problem. The findings highlight the importance of Fbp2 in thermal regulation under fasting conditions.

The mutant allele of rice calmodulin-binding transcription activator OsCBT, oscbt-1, exhibits broad-spectrum resistance against rice pathogens. Previously, we reported that the strong resistance of the oscbt-1 mutant to pathogens was conferred by a constitutive upregulation of defense-related genes even under pathogen-free conditions. We also found strong induction of the hypersensitive response as a reaction to pathogen invasion. The results suggest that OsCBT acts as a negative regulator of basal resistance to pathogen attack. To identify the transcriptional network regulated by OsCBT, we compared global gene expression profiles between wild-type (WT) and oscbt-1 rice plants grown under pathogen-free conditions. The results of a 3′ tiling microarray revealed that in oscbt-1 plants, 81 genes are upregulated and 200 genes are downregulated when compared with the WT. A gene ontology analysis showed that differentially regulated genes in oscbt-1 were very closely associated with “death” GO term in a biological process category, and “catalytic activity” and “binding” GO terms in a molecular function category. A MapMan analysis indicated that the functions of these genes were associated with plant responses to biotic stress. Moreover, the results from quantitative real-time PCR in the oscbt-1 mutant showed a significant effect on the gene expression patterns of the fungal pathogen response. Our results suggested that the OsCBT regulates a rice defense response by modulating the expressions of various defense-related genes.

Chronic alcohol feeding increases the levels of 2-arachidonoylglycerol (2-AG) in the liver, which activates hepatic cannabinoid receptor type 1 (CB1R), leading to oxidative liver injury. 2-AG biosynthesis is catalyzed by diacylglycerol lipase (DAGL). However, the mechanisms regulating hepatic DAGL gene expression and 2-AG production are largely unknown. In this study, we show that CB1R-induced estrogen-related receptor γ (ERRγ) controls hepatic DAGL gene expression and 2-AG levels. Arachidonyl-2'-chloroethylamide (ACEA), a synthetic CB1R agonist, significantly upregulated ERRγ, DAGLα, and DAGLβ, and increased 2-AG levels in the liver (10 mg/kg) and hepatocytes (10 μM) of wild-type (WT) mice. ERRγ overexpression upregulated DAGLα and DAGLβ expressions and increased 2-AG levels, whereas ERRγ knockdown abolished ACEA-induced DAGLα, DAGLβ, and 2-AG in vitro and in vivo. Promoter assays showed that ERRγ positively regulated DAGLα and DAGLβ transcription by binding to the ERR response element in the DAGLα and DAGLβ promoters. Chronic alcohol feeding (27.5% of total calories) induced hepatic steatosis and upregulated ERRγ, leading to increased DAGLα, DAGLβ, or 2-AG in WT mice, whereas these alcohol-induced effects did not occur in hepatocyte-specific CB1R knockout mice or in those treated with the ERRγ inverse agonist GSK5182 (40 mg/kg in mice and 10 μM in vitro). Taken together, these results indicate that suppression of alcohol-induced DAGLα and DAGLβ gene expressions and 2-AG levels by an ERRγ-specific inverse agonist may be a novel and attractive therapeutic approach for the treatment of alcoholic liver disease.

Rehmannia glutinosa (family Scrophulariaceae) is a widely used traditional medicinal plant with increasing area under cultivation. In Korea, five viruses have been reported to infect R. glutinosa: broad bean wilt virus 2 (BBWV2), Plantago asiatica mosaic virus (PlAMV), Rehmannia mosaic virus (ReMV), ribgrass mosaic virus (RMV), and youcai mosaic virus (YoMV). Here, we developed a one-step multiplex RT-PCR method for simultaneous detection of BBWV2, PlAMV, ReMV, and subgroup3 tobamoviruses (RMV and YoMV), providing a rapid, convenient, cost-efficient method to detect multiple R. glutinosa viruses.

Watermelon (Citrullus lanatus) is one of the most popular crops in Korea, with over 100 million units produced annually. As watermelon cultivation increases, the damage caused by plant viruses in watermelon farms is also increasing. In July 2020, some watermelons cultivated on farms in Uiryeong showed typical viral symptoms, such as yellowing and necrosis. In previous studies, two plant viruses, cucurbit aphid-borne yellows virus (CABYV) and cucurbit chlorotic yellows virus (CCYV), have been reported as causal agents of yellowing disease in the cucurbitaceae plant in Korea. To identify the virus(es) associated with the symptomatic watermelon plants, 11 samples were collected. Total RNA was extracted from each sample using the Plant RNA Prep kit (Biocube System, Gwacheon, Korea). RT-PCR was performed using primer sets specific to CABYV and CCYV to detect each virus (Kwak et al. 2018, Wintermantel et al. 2019). CABYV was detected in one sample, and CCYV was detected in 8 samples. Every sample presented similar yellowing symptoms; however, neither virus was detected in the remaining two samples. To investigate unknown viruses, a transcriptome library was constructed using total RNA of the watermelons and sequenced using a NovaSeq 6000 sequencer (Illumina, San Diego, CA). The reads were de novo assembled and annotated using the KEGG virus genome database with the NCBI BLAST utility. All procedures of next generation sequencing were performed by Macrogen (Seoul, Korea). Three large viral contigs were identified, and additional BLAST analyses for nucleotides (nt) and proteins indicated that they were CABYV, CCYV, and melon aphid-borne yellows virus (MAYBV). A total of 247,198 reads were mapped to reference MABYV sequence (GenBank Accession Number NC_010809), and the sequencing depth was 6,575X. The contig (MW505927) had a size of 5,677 nt and showed 100% coverage and 96% identity with known complete MABYV sequences (JQ700307 and EU000534). To confirm the presence of MABYV, RT-PCR was performed using specific primer sets targeting MABYV (MABYV-262-F, 5'-GAACCGTCGACGCACTTCAAAGAGTA-3' and Polero-uni-R, 5'-GATYTTATAYTCATGGTAGGCCTTGAG-3'; Knierim et al. 2010). The expected size of 262 bp was obtained from 5 out of 11 samples, including the two samples mentioned above. MABYV belongs to the genus Polerovirus and has been reported in cucurbit crops in China, Taiwan, and Thailand (Xiang et al. 2008, Knierim et al. 2010, Cheewachaiwit et al. 2017). According to the farmer, outbreak of aphids had previously occurred and were controlled with pesticides. Since aphids are known to be vectors of poleroviruses, we surmise that the watermelons were infected with MABYV by the aphids at that time. To monitor the outbreak of MABYV, watermelon farms in Uiryeong will be continuously investigated. To our knowledge, this is the first report of MABYV in Korea.

Equine parvovirus-cerebrospinal fluid (EqPV-CSF) and eqcopivirus (EqCoPV) are new parvovirus species (EqPVs) identified from various tissues (CSF, blood, and respiratory swabs) in horses with neurologic and respiratory diseases. In this study, we described the prevalence rate of EqPV-CSF and EqCoPV in 133 and 77 serum and fecal samples, respectively, using polymerase chain reaction. Further, we analyzed the potential risk factors for infection. We calculated the nucleotide and amino acid similarity and constructed phylogenetic trees. There was a moderate-to-high prevalence rate (EqPV-CSF: 3.8%, EqCoPV 9.8%) of each virus in serum, moreover, age, country of foaling, and clinical colic signs were significantly associated with the EqPVs infection. The newly identified EqPV-CSF/EqCoPV genomes had high nucleotide and amino acid identities with previously isolated strains in the USA. In phylogenetic analysis, they clustered and formed a new subgroup in the genus Copiparvovirus. To our knowledge, this is the first field epidemiologic study on EqPV-CSF and EqCoPV using both serum and fecal samples. Our findings demonstrate the risk factors for infection and could facilitate the development of disease prevention strategies.

Simple Summary Spotted wing Drosophila, Drosophila suzukii, is an important quarantine pest in Korea due to its oviposition behavior. In this study, insecticidal effects of methyl bromide (MB) alone and successive application of methyl bromide and cold treatment were compared to examine their potential to reduce methyl bromide usage and shorten the cold treatment periods. Eggs, larvae, and pupae were subjected to treatment with fumigants to determine the 50 and 99% lethal concentration time values. The results show that, through treatment with methyl bromide plus cold, control can be achieved at lower concentrations than for treatment with methyl bromide alone and with shorter treatment periods than for treatment with cold treatment alone. Phytotoxic effects from successive treatment on strawberry were not observed. Therefore, methyl bromide plus cold treatment can effectively control D. suzukii in strawberry without damage to fresh fruits. Abstract Recently, spotted wing Drosophila, Drosophila suzukii, is globally prevalent and causes agricultural losses to many fruits. To export Korean strawberry, methyl bromide fumigation is required to remove D. suzukii infestations, but Korean strawberry farmers are worried about fruit damage because methyl bromide can cause phytotoxicity on fresh commodities. In this report, we assessed the efficacy and phytotoxicity of single and successive application of methyl bromide and cold treatment on an export variety of strawberry to reduce fruit damage. The currently recommended dosage of methyl bromide, 40 g/m3 for 3 h at 18 °C, was enough to control all stages of D. suzukii without phytotoxicity. A dosage of 20 g/m3 of methyl bromide treatment for 3 h, followed by 1 d of cold (0 °C) treatment, showed 100% mortality in all growth stages of D. suzukii without fruit damage. Successive application of methyl bromide and cold treatment shows potential as a method of decreasing phytotoxicity and reducing the use of methyl bromide for environmental considerations.

MyTH4-FERM (MF) myosins evolved to play a role in the creation and function of a variety of actin-based membrane protrusions that extend from cells. Here we performed an analysis of the MF myosins, Myo7A, Myo7B, and Myo10, to gain insight into how they select for their preferred actin networks. Using enterocytes that create spatially separated actin tracks in the form of apical microvilli and basal filopodia, we show that actin track selection is principally guided by the mode of oligomerization of the myosin along with the identity of the motor domain, with little influence from the specific composition of the lever arm. Chimeric variants of Myo7A and Myo7B fused to a leucine zipper parallel dimerization sequence in place of their native tails both selected apical microvilli as their tracks, while a truncated Myo10 used its native antiparallel coiled-coil to traffic to the tips of filopodia. Swapping lever arms between the Class 7 and 10 myosins did not change actin track preference. Surprisingly, fusing the motor-neck region of Myo10 to a leucine zipper or oligomerization sequences derived from the Myo7A and Myo7B cargo proteins USH1G and ANKS4B, respectively, re-encoded the actin track usage of Myo10 to apical microvilli with significant efficiency.

Mycoplasma synoviae (MS) is an avian pathogen that causes respiratory disease, infectious synovitis, and eggshell apex abnormalities in chickens. Nicotinamide adenine dinucleotide (NAD)-independent MS was first reported in 1975. Despite the atypical traits of NAD-independent MS, its independence from NAD has not been studied. In this study, we isolated five NAD-independent strains from Korea and assembled their genomes using sequencing reads obtained from Illumina and Oxford Nanopore Technology platforms. The assembled genomes were compared with the genomes of MS-H vaccine strain and type strain WVU1853. We found that the coding sequences of nicotinate phosphoribosyltransferase and glycerol-3-phosphate acyltransferase, and a unique coding sequence were present only in the genomes of NAD-independent isolates.

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne’s disease (JD), and it causes diarrhea and weakness in cattle. During a long subclinical stage, infected animals without clinical signs shed pathogens through feces. For this reason, the diagnosis of JD during the subclinical stage is very important. Circulating miRNAs are attracting attention as useful biomarkers in various veterinary diseases because of their expression changes depending on the state of the disease. Based on current knowledge, circulating miRNAs extracted from bovine serum were used to develop a diagnostic tool for JD. In this study, the animals were divided into 4 groups according to fecal shedding, the presence of antibodies, and clinical signs. Gene expression was analyzed by performing miRNA sequencing for each group, and it was identified that the miRNA expression changed more as the MAP infection progressed. The eight miRNAs that were differentially expressed in all infected groups were selected as biomarker candidates based on their significant differences compared to the control group. These biomarker candidates were validated by qRT-PCR. Considering the sequencing data, two upregulated miRNAs and two downregulated miRNAs showed the same trend in the validation results. Network analysis was also conducted and the results showed that mRNAs (IL-10, TGF-β1) associated with regulatory T cells were predicted to be activated in the subclinical stage. Taken together, our data suggest that two miRNAs (bta-miR-374b, bta-miR-2887) may play major roles in the immune response to MAP infection during the subclinical stage.

Simple Summary The more the global agricultural product trade becomes active every year, the more foreign pests’ invasion probability increases. Accordingly, many notorious invasive pests are spreading worldwide, and the nations should try to block their introduction through quarantine systems. As an important quarantine pest, the oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae), is one of the most destructive pest insects for fruit crops in tropical and subtropical areas. This species is a highly invasive and economically important pest with a broad host range. Here, we collected 40 geographically or temporally different collections from 12 Asian countries, including four from the Korean border quarantine detection, and performed haplotype analysis and population genetics analysis. Abstract To infer the introduction sources of the oriental fruit fly, Bactrocera dorsalis, we used a mitochondrial marker to reconstruct the haplotype network and 15 microsatellite loci to reveal genetic structure and relationships between the geographically or temporally different collections from Asia. We performed Approximate Bayesian computations to infer a global origin and a source of the quarantine collections found in Korea. As a result, the 40 populations were divided into three groups, of which genetic similarity is not related to the geographic vicinity. Korean samples had a similar genetic structure to Taiwan and Thailand ones. Our results suggest that the place of origin of the B. dorsalis specimens found in Korea’s border quarantine is likely to be Taiwan or Thailand. As the global origin of B. dorsalis, we estimated that Taiwan and Thailand were most likely the global origins of Southeast Asian populations by testing hypothetical scenarios by the approximate Bayesian computation analyses. Our results will allow easier identification of the source region of the forthcoming invasion of quarantined B. dorsalis specimens.

O-linked-N-acetylglucosaminylation (O-GlcNAcylation) performed by O-GlcNAc transferase (OGT) is a nutrient-responsive post-translational modification (PTM) via the hexosamine biosynthetic pathway (HBP). Various transcription factors (TFs) are O-GlcNAcylated, affecting their activities and significantly contributing to cellular processes ranging from survival to cellular differentiation. Given the pleiotropic functions of O-GlcNAc modification, it has been studied in various fields, however, the role of O-GlcNAcylation during osteoclast differentiation remains to be explored. Kinetic transcriptome analysis during receptor activator of nuclear factor-kappaB (NF-κB) ligand (RANKL)-mediated osteoclast differentiation revealed that the nexus of major nutrient metabolism, HBP was critical for this process. We observed that the critical genes related to HBP activation, including Nagk, Gfpt1, and Ogt, were upregulated, while the global O-GlcNAcylation was increased concomitantly during osteoclast differentiation. The O-GlcNAcylation inhibition by the small-molecule inhibitor OSMI-1 reduced osteoclast differentiation in vitro and in vivo by disrupting the translocation of NF-κB p65 and nuclear factor of activated T cells c1 (NFATc1) into the nucleus by controlling their PTM O-GlcNAcylation. Furthermore, OSMI-1 had a synergistic effect with bone target therapy on osteoclastogenesis. Lastly, knocking down Ogt with shRNA (shOgt) mimicked OSMI-1’s effect on osteoclastogenesis. Targeting O-GlcNAcylation during osteoclast differentiation may be a valuable therapeutic approach for osteoclast-activated bone diseases.

Hepatitis A virus (HAV), the causative pathogen of hepatitis A, induces severe acute liver injuries in humans and is a serious public health concern worldwide. However, appropriate therapeutics have not yet been developed. The enzyme heme oxygenase-1 (HO-1) exerts antiviral activities in cells infected with several viruses including hepatitis B and C viruses. In this study, we demonstrated for the first time the suppression of virus replication by HO-1 in cells infected with HAV. Hemin (HO-1 inducer) induced HO-1 mRNA and protein expression, as expected, and below 50 mM, dose-dependently reduced the viral RNA and proteins in the HAV-infected cells without cytotoxicity. Additionally, HO-1 protein overexpression using a protein expression vector suppressed HAV replication. Although ZnPP-9, an HO-1 inhibitor, did not affect HAV replication, it significantly inhibited hemin-induced antiviral activity in HAV-infected cells. Additionally, FeCl3, CORM-3, biliverdin, and the HO-1 inducers andrographolide and CoPP inhibited HAV replication in the HAV-infected cells, andrographolide and CoPP exhibited a dose-dependent effect. In conclusion, these results suggest that HO-1 effectively suppresses HAV infection in vitro, and its enzymatic products appear to exert antiviral activity. We expect that these results could contribute to the development of a new antiviral drug for HAV.

Several animal species including pigs are directly involved in the zoonotic transmission of the hepatitis E virus (HEV) to humans. This study was conducted to detect HEV in bovine and porcine raw livers by nested reverse transcription-polymerase chain reaction. Zoonotic HEV strains were identified in 1.0 and 3.0% of the tested bovine and porcine livers, respectively. HEV-4 was detected in the bovine livers, but both HEV-3 and HEV-4 were identified in the porcine livers. These results indicate that zoonotic transmission of HEV may occur via consumption of raw or undercooked livers of pigs and cattle.

This report reveals the structure of a virus extracted from the Korean horn beetle Allomyrina dichotoma. The purified virus particle was 100% identical to Allomyrina virus lef‐8 sequence registered as KM_233709.1. The structure of this virus was confirmed to be closely related to that of the Nudiviridae family, and it was rod shaped and enveloped, and observed to be of approximately the mean length of a single viral nucleocapsid of 200–210 nm and mean diameter of 100–110 nm. These results provide an insight into the structural characteristics of the Nudiviridae family that can be used for nudiviral identification.

A Gram-stain-negative, strictly aerobic, non-motile, rod-shaped bacterial strain, designated strain DSW4-44T, was isolated from deep-sea water from the East Sea of Korea. The optimum temperature and pH for growth were 25 °C and pH 7.5. DSW4-44T grew with 1.0–6.0 % NaCl, having optimum growth at 3–4 %. Phylogenetic analyses based on 16S rRNA gene sequences indicated that DSW4-44T represented a member of the class Alphaproteobacteria and was most closely related to Pelagicola litoralis CL-ES2T and Pelagicola litorisediminis D1-W8T, with similarities of 96.5 and 95.6 %, respectively. The major fatty acid was summed feature 8 (comprising C18 : 1ω7c and/or C18 : 1ω6c). The polar lipids of DSW4-44T were phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, an unidentified aminolipid, two unidentified lipids and three unidentified phospholipids. The isoprenoid quinone was Q-10. The DNA G+C content of DSW4-44T was 54.3 mol%. On the basis of evidence from a polyphasic study, strain DSW4-44T represent a novel species of the genus Pelagicola , for which the name Pelagicola marinus sp. nov. is proposed. The type strain is DSW4-44T (=KCTC 62762T=KCCM 43261T=JCM 33637T).

Background A new approach targeting aeroallergen sensing in the early events of mucosal immunity could have greater benefit. The CSF1-CSF1R pathway has a critical role in trafficking allergens to regional lymph nodes through activating dendritic cells. Intervention in this pathway could prevent allergen sensitization and subsequent Th2 allergic inflammation. Objective To examine the therapeutic effectiveness of CSF1 and CSF1R inhibition for blocking the dendritic cell function of sensing aeroallergens. Methods We adopted a model of chronic asthma induced by a panel of three naturally occurring allergens and novel delivery system of CSF1R inhibitor encapsulated nanoprobe. Results Selective depletion of CSF1 in airway epithelial cells abolished the production of allergen-reactive IgE, resulting in prevention of new asthma development as well as reversal of established allergic lung inflammation. CDPL-GW nanoprobe containing GW2580, a selective CSF1R inhibitor, showed favorable pharmacokinetics for inhalational treatment and intranasal insufflation delivery of CDPL-GW nanoprobe ameliorated asthma pathologies including allergen-specific serum IgE production, allergic lung and airway inflammation and airway hyper-responsiveness (AHR) with minimal pulmonary adverse reaction. Conclusion The inhibition of the CSF1-CSF1R signaling pathway effectively suppresses sensitization to aeroallergens and consequent allergic lung inflammation in a murine model of chronic asthma. CSF1R inhibition is a promising new target for the treatment of allergic asthma.

We reared the cross-bred FD lineage (F♀ × D♂) from inbred lines in pursuit of high royal jelly (RJ)-producing honeybee traits. The present study compared the new crossbred FD line to a high RJ-producing colony (HRC) and a low RJ-producing colony (LRC) by investigating the production of RJ, morphological characteristics, and age-dependent hypopharyngeal gland (HPG) development of the honeybees. The HRC exhibited the highest RJ production (416.46 ± 71.49 mg/cup), followed by the FD (369.29 ± 80.89 mg/cup), and the LRC (284.79 ± 38.54 mg/cup) colonies, respectively. The 10-HDA content was highest in the FD colony (2.38%), followed by the LRC (2.06%) and the HRC (1.91%). Compared to newly emerged bees, the body weight, fresh head weight, and HPG development increased until 9 days, and then decreased thereafter. Moreover, the length of the acini of the HPG at 9 days-old was almost twice as long than those of the bees at first emergence in all colonies. The acini diameters of the HPG in the HRC were significantly larger at all age stages. Compared to the LRC line, the acini in the FD line were significantly longer until 9 days after hatching. The abdominal length and forewing length were longer in the HRC, while the corbicular area, and head, proboscis, and glossa lengths were longer in the FD. The discriminant function analysis revealed that 78.1% of the individuals were classified correctly. Further assessements of wing geometric morphometrics are needed to clarify the morphological characteristics of the new hybrid FD line with high RJ-producing traits.

Infection with hepatitis E virus (HEV) has raised serious public health concerns worldwide. In this study, a nanogel-based vaccine encapsulating the capsid protein of rabbit HEV was developed and its protective efficacy was compared with a subunit vaccine. A total of 23 rabbits were divided into 5 groups: (1) negative control (n = 4), (2) positive control (n = 4), (3) nanogel control (n = 5), (4) nanogel vaccine (n = 5), and (5) subunit vaccine (n = 5). Rabbits were vaccinated two times, at weeks 0 and 1, with nanogel and subunit vaccines, respectively, and challenged with rabbit HEV at week 4. By week 11, rabbits vaccinated with the nanogel vaccine produced higher antibodies than those vaccinated with the subunit vaccine. Fecal viral shedding and viremia were identified in rabbits of the positive and nanogel control groups at weeks 6-10. However, there was no viral shedding and viremia in rabbits immunized with both the nanogel and subunit vaccines. Alanine aminotransferase and aspartate aminotransferase levels were not elevated in any rabbit. However, histopathological examination revealed much less hepatic inflammation in rabbits of the nanogel vaccine group compared to the positive and nanogel control groups. Significant increases in IL-12 and IFN-γlevels were identified from rabbits immunized with the nanogel vaccine. Collectively, these results indicate that the newly developed nanogel vaccine induced sufficient immunity leading to complete protection from HEV infection in rabbits. Application of this vaccine should be considered as a preventive measure against HEV infection in other animal species and humans.

Background Skeletal muscle atrophy is defined as a reduction of muscle mass caused by excessive protein degradation. However, the development of therapeutic interventions is still in an early stage. Although glucagon‐like peptide‐1 receptor (GLP‐1R) agonists, such as exendin‐4 (Ex‐4) and dulaglutide, are widely used for the treatment of diabetes, their effects on muscle pathology are unknown. In this study, we investigated the therapeutic potential of GLP‐1R agonist for muscle wasting and the mechanisms involved. Methods Mouse C2C12 myotubes were used to evaluate the in vitro effects of Ex‐4 in the presence or absence of dexamethasone (Dex) on the regulation of the expression of muscle atrophic factors and the underlying mechanisms using various pharmacological inhibitors. In addition, we investigated the in vivo therapeutic effect of Ex‐4 in a Dex‐induced mouse muscle atrophy model (20 mg/kg/day i.p.) followed by injection of Ex‐4 (100 ng/day i.p.) for 12 days and chronic kidney disease (CKD)‐induced muscle atrophy model. Furthermore, we evaluated the effect of a long‐acting GLP‐1R agonist by treatment of dulaglutide (1 mg/kg/week s.c.) for 3 weeks, in DBA/2J‐mdx mice, a Duchenne muscular dystrophy model. Results Ex‐4 suppressed the expression of myostatin (MSTN) and muscle atrophic factors such as F‐box only protein 32 (atrogin‐1) and muscle RING‐finger protein‐1 (MuRF‐1) in Dex‐treated C2C12 myotubes. The suppression effect was via protein kinase A and protein kinase B signalling pathways through GLP‐1R. In addition, Ex‐4 treatment inhibited glucocorticoid receptor (GR) translocation by up‐regulating the proteins of GR inhibitory complexes. In a Dex‐induced muscle atrophy model, Ex‐4 ameliorated muscle atrophy by suppressing muscle atrophic factors and enhancing myogenic factors (MyoG and MyoD), leading to increased muscle mass and function. In the CKD muscle atrophy model, Ex‐4 also increased muscle mass, myofiber size, and muscle function. In addition, treatment with a long‐acting GLP‐1R agonist, dulaglutide, recovered muscle mass and function in DBA/2J‐mdx mice. Conclusions GLP‐1R agonists ameliorate muscle wasting by suppressing MSTN and muscle atrophic factors and enhancing myogenic factors through GLP‐1R‐mediated signalling pathways. These novel findings suggest that activating GLP‐1R signalling may be useful for the treatment of atrophy‐related muscular diseases.