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This study applied a molecular-based method to detect parainfluenza virus 5 (PIV5) collected from 2016 to 2018 in nine provinces of Republic of Korea. We demonstrated that PIV5 was detectable in both serum and pooled organs at an average positive rate of 1.78% (99/5566). Among these, the complete genome sequence of 15,246 nucleotides was obtained for 12 field strains. Three out of the 12 strains had the lowest genetic identity (96.20–96.68%) among the 21 porcine PIV5 genomes collected in Germany, China, India, and Republic of Korea from 1998 to 2017. By analyzing a large collection of complete genome sequences of the structural protein-coding F and HN genes, this study proposed a classification of PIV5 into two lineages, 1 and 2, and identified that group 2.2.2 within sub-lineage 2.2 was substantially divergent. The evolution of two structural protein-coding genes was largely under purifying selection. A few codons (6/9 for the F gene, 7/8 for the HN gene) had elevated dN/dS values, which were loaded on internal branches and were predicted to be related to beneficial trait(s) of the virus.

Dysregulation of the ubiquitin-proteasome system has been implicated in the pathogenesis of several metabolic disorders, including obesity, diabetes, and non-alcoholic fatty liver disease; however, the mechanisms controlling pathogenic metabolic disorders remain unclear. Transcription factor CCAAT/enhancer binding protein beta (C/EBPβ) regulates adipogenic genes. The study showed that the expression level of C/EBPβ is post-translationally regulated by the deubiquitinase ubiquitin-specific protease 1 (USP1) and that USP1 expression is remarkably upregulated during adipocyte differentiation and in the adipose tissue of mice fed a high-fat diet (HFD). We found that USP1 directly interacts with C/EBPβ. Knock-down of USP1 decreased C/EBPβ protein stability and increased its ubiquitination. Overexpression of USP1 regulates its protein stability and ubiquitination, whereas catalytic mutant of USP1 had no effect on them. It suggests that USP1 directly deubiquitinases C/EBPβ and increases the protein expression, leading to adipogenesis and lipid accumulation. Notably, the USP1-specific inhibitor ML323—originally developed to sensitize cancer cells to DNA-damaging agents—decreased adipocyte differentiation and lipid accumulation in 3T3-L1 cells without cytotoxicity. Oral gavage of ML323 was administered to HFD-fed mice, which showed weight loss and improvement in insulin and glucose sensitivity. Both fat mass and adipocyte size in white adipose tissues were significantly reduced by ML323 treatment, which also reduced expression of genes involved in adipogenesis and inflammatory responses. ML323 also reduced lipid accumulation, hepatic triglycerides, free fatty acids, and macrophage infiltration in the livers of HFD-fed mice. Taken together, we suggest that USP1 plays an important role in adipogenesis by regulating C/EBPβ ubiquitination, and USP1-specific inhibitor ML323 is a potential treatment option and further study by ML323 is needed for clinical application for metabolic disorders.

Figure S1. The basal mRNA expression level of HMMR in the gastric cancer cell line. Figure S2. Indirect regulation of transcription activity with galectin-3. Figure S3. Detection of mRNA and protein expression level of C/EBP family with galectin-3. Figure S4. Detection of mRNA and protein expression of HMMR with C/EBPβ overexpression. Supplementary Table 1. List of gene ontology significantly upregulated by galectin-3 silencing in AGS cells Supplementary Table 2. List of gene ontology significantly downregulated by galectin-3 silencing in AGS cells Supplementary Table 3. List of upregulated genes related to cell progression and cell motility with galectin-3 silencing in AGS cells Supplementary Table 4. List of downregulated genes related to cell progression and cell motility with galectin-3 silencing in AGS cells

Symptomatic ganglion cysts within the knee joint are rare, and the mainstay of treatment for these cases has been surgical excision. We present a case of a ganglion cyst of the anterior cruciate ligament (ACL) treated with ultrasound-guided aspiration in an outpatient clinic. A 45-year-old woman presented to the hospital with posterior right knee pain after falling down. We were able to identify well circumscribed 2.2cm mass confined to ACL on Magnetic resonance imaging (MRI). We performed percutaneous needle aspiration of the ACL ganglion cyst under ultrasound (US) guidance. The patient's symptoms improved immediately after the procedure and she had no complications. Four weeks later, follow-up revealed that the patient's symptoms had disappeared. Six months later, a recurrence of a ganglion cyst was confirmed on follow-up and was treated in the same way.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer; however, specific prognostic biomarkers have not yet been developed. In this study, we identified dysregulated microRNAs (miRNAs) in TNBC by profiling miRNA and mRNA expression. In patients with TNBC, miR-371b-5p expression was reduced, and miR-371b-5p overexpression significantly mitigated TNBC cell growth, migration, and invasion. In addition, we found that expression of cold shock domain-containing protein E1 (CSDE1), a direct target gene of miR-371b-5p, was upregulated in TNBC cells, and inhibition of CSDE1 expression alleviated TNBC cell growth by regulating RAC1 transcription. Mechanistically, CSDE1, phosphorylated C-terminal domain (p-CTD) of RNA polymerase II (RNAPII), and CDK7 form a complex, and downregulation of CSDE1 leads to weak interaction between RNAPII p-CTD and CDK7, resulting in a decrease in RNAPII p-CTD expression to reduce RAC1 transcript levels in CSDE1-deficient TNBC cells. Our data demonstrate that miR-371b-5p is a tumor-suppressive miRNA that regulates the CSDE1/Rac1 axis and could be a potential prognostic biomarker for TNBC.

Bacillus amyloliquefaciens is a gram-positive bacterial species that is utilised as a probiotic in humans and animals. There are no reports of infective endocarditis (IE) in dogs. An 8-year-old, spayed, female Maltese presented with a 1-month history of fever, depression, weight loss, and hindlimb lameness. Laboratory test results indicated non-regenerative anaemia, neutrophilia, hyperglobulinemia, and proteinuria. Echocardiography revealed vegetation on the septal leaflet of the mitral valve and thromboemboli in the left atrium. Consecutive blood culture results revealed that the blood samples were consistently positive for Bacillus amyloliquefaciens, which is generally considered a probiotic bacterial species for animals. Broad-spectrum antibiotics (amoxicillin-clavulanic acid and cefotaxime) and anticoagulants (clopidogrel and rivaroxaban) were administered for 4 months. The clinical signs were responsive to antibiotic treatment. After 4 months, the dog was no longer febrile and the size of the thromboemboli in the left atrium had decreased. Bacteria were no longer isolated in blood cultures after antibiotic therapy. To the best of our knowledge, this is the first case report of canine IE caused by bactaeremic infection with Bacillus amyloliquefaciens.

Supplementary figure legends

Supplementary Table S1: Immunohistochemical staining of Notch1-IC and HIPK2 in serial tissue arrays of 61 breast cancer samples. Supplementary Table S2: Semi-Quantitative analysis of Notch1-IC, phosphorylated Notch1-IC T2512, HIPK2, and Fbw7 expression in breast cancer tissues.

Description of additional methods and procedures used in the study.

Supplementary Figure 1: ADR suppresses Notch1 signaling. Supplementary Figure 2: ADR inhibits the transcriptional activity of Notch1 by inducing HIPK2. Supplementary Figure 3: HIPK2 regulates the Notch1-IC protein stability through proteasomal degradation pathways. Supplementary Figure 4: HIPK2 facilitates Notch1-IC degradation by Fbw7 ubiquitin ligase. Supplementary Figure 5: HIPK2 physically interacts with Notch1-IC. Supplementary Figure 6: HIPK2 phosphorylates Notch1-IC at the T2512 residue. Supplementary Figure 7: HIPK2-mediated downregulation of Notch1-IC suppresses the tumorigenesis of breast cancer. Supplementary Figure 8: Somatic mutations in the CPD motif of Notch1-IC make it resistant to HIPK2. Supplementary Figure 9: Physiological effects of somatic mutations in the CPD motif of Notch1-IC. Supplementary Figure 10: A propose model of Notch1 signaling pathway regulation by HIPK2 in cancer during chemotherapy.

The receptor Notch1 plays an important role in malignant progression of many cancers, but its regulation is not fully understood. In this study, we report that the kinase HIPK2 is responsible for facilitating the Fbw7-dependent proteasomal degradation of Notch1 by phosphorylating its intracellular domain (Notch1-IC) within the Cdc4 phosphodegron motif. Notch1-IC expression was higher in cancer cells than normal cells. Under genotoxic stress, Notch1-IC was phosphorylated constitutively by HIPK2 and was maintained at a low level through proteasomal degradation. HIPK2 phosphorylated the residue T2512 in Notch1-IC. Somatic mutations near this residue rendered Notch1-IC resistant to degradation, as induced either by HIPK2 overexpression or adriamycin treatment. In revealing an important mechanism of Notch1 stability, the results of this study could offer a therapeutic strategy to block Notch1-dependent progression in many types of cancer. Cancer Res; 76(16); 4728–40. ©2016 AACR.

Supplementary Figure 3. The relationship between Notch1 and miR-34 family members.

Supplementary Figure 4. Overexpression of miR-34a by lentiviral system in primary cells.

Supplementary Methods, Figure Legends

Supplementary Figure 1. Expression levels of cancer stem cell markers in tumorsphere cells.

Supplementary Figure 2. Expression levels of Notch family in tumorsphere cells.

The safety of the probiotic strain Q180, which exerts postprandial lipid-lowering effects, was bioinformatically and phenotypically evaluated. The genome of strain Q180 was completely sequenced, and single circular chromosome of 3,197,263 bp without any plasmid was generated. Phylogenetic and related analyses using16S rRNA gene and whole-genome sequences revealed that strain Q180 is a member of Lactiplantibacillus (Lp., formerly Lactobacillus) plantarum. Antimicrobial resistance (AMR) genes were bioinformatically analyzed using all Lp. plantarum genomes available in GenBank, which showed that AMR genes are present differently depending on Lp. plantarum strains. Bioinformatic analysis demonstrated that some mobile genetic elements such as prophages and insertion sequences were identified in the genome of strain Q180, but because they did not contain harmful genes such as AMR genes and virulence factor (VF)- and toxin-related genes, it was suggested that there is no transferability of harmful genes. The minimum inhibition concentrations of seven tested antibiotics suggested by the European Food Safety Authority guidelines were slightly lower than or equal to the microbiological cut-off values for Lp. plantarum. Strain Q180 did not show hemolytic and gelatinase activities and biogenic amine-producing ability. Taken together, this study demonstrated the safety of strain Q180 in terms of absence of AMR genes and VF- and toxin-related genes as a probiotic strain.

Coronavirus is causing many diseases and economic pain to humans and animals. The present study demonstrated how ultra weak lightcause changes in porcine epidemic diarrhea virus (PEDV) and Vero cells. Ultra weak lightactivates Vero cells by lowering pH of maintain media, but have proven no effect of killing the virus.