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Ag has the lowest stacking fault energy of all metals, which allows twin formation to occur more easily. The (111)-preferred orientation Ag nanotwinned films is fabricated by either sputtering or evaporation method exhibit columnar Ag grains grown vertically on Si substrates. Ag nanotwinned films have a (111)-preferred orientation with a density about 98% and diffusivity that is 2 to 5 orders of magnitude higher than those of (100) and (110) surfaces. Low temperature direct bonding with (111)-oriented Ag nanotwins films is proposed to fulfil the requirements for wafer-on-wafer (WoW), chip-on-wafer (CoW), and chip-on-wafer-on-substrate (CoWoS) advanced 3D-IC packaging, with the process temperature drastically reduced to 100°C. Such an innovative bonding method also provides a promising solution for die attachment of Si chips with DBC-ceramic substrates for power module packaging.

In this study, a novel method for producing high-density 〈111〉-oriented nanotwinned Ag film is proposed so as to improve the performance of backside metallization for power devices. Negative bias voltages were applied during sputtering to facilitate the formation of densely stacked nanotwinned columnar structures. In addition, the effects of substrate bias on the properties of Ag films were observed in the lower transition layer thickness, stronger 〈111〉 texture, and higher indentation hardness. The optimal indentation hardness, 1.71 GPa, was found in the nanotwinned Ag film sputtered with a bias voltage of − 150 V; it was about twice that of the normal-grained Ag film sputtered without substrate bias, 0.85 GPa. In addition, the results showed that the Ag film sputtered with a bias voltage of − 150 V possessed the strongest (111) intensity, and its surface (111) ratio was 98%, much higher than the 77% of the Ag film sputtered without substrate bias. It is concluded that the Ag nanotwinned film sputtered with a bias voltage of − 150 V has the potential for application as an interlayer in low-temperature direct bonding.

Considering the importance of the canine cancer model of human disease, as well as the need for strategies for canine cancer management, the properties of exosomes are an emerging topic in canine oncology. In our study, exosomal RNA was isolated and investigated by next-generation sequencing. We identified several differentially expressed microRNAs (miRNAs/miRs) in the exosomes of two melanoma cell lines compared with non-tumor reference exosomes. We explored these potential melanoma-specific exosomal miRNAs further and found that miR-143 and let-7b increased in primary, whereas miR-210, 708, 221, and 222 increased in metastatic site originated melanoma cells. Further analysis showed miR-143 and 221 significantly increased in plasma exosomes of metastatic melanoma patients. Moreover, the sensitivity and specificity are >85% for differentiating the non-metastatic and metastatic patients. Therefore, these miRNAs can be an incredible biomarker candidate to identify metastatic melanoma and facilitate a better prognosis.

For improving the performance of backside metallization for power electronic devices, an innovative Ag film with ultra-high twin density is proposed in this study. Experimentally, nanotwinned Ag films with thicknesses ranging from 2 to 8 µm and a strong (111) preferred orientation were sputtered on Si (100) wafers with and without a Ti thin film. The results indicated that the coincident Σ3 twin and Σ9 near-twin boundaries in proportion to the total grain boundaries in this Ag nanotwinned film on Ti pre-coated Si (100) wafer were 50.8 % and 13.5 %, respectively. These Ag nanotwins had spacing of 2 to 50 nm, with an average spacing of about 12 nm, and were contained in columnar Ag grains grown normal to the Si wafer. The employment of a Ti interlayer of 0.1 µm thickness clearly improved the adhesion at the Ag/Si interface under peeling tests, resulting in a bonding strength of 1.7 MPa and a maximal indentation hardness of 2 GPa.

Background/aim The number of vertebrae in swine varies from 19 to 23 and is associated with body size. Nuclear receptor subfamily 6 group A member 1 (NR6A1) is considered a strong candidate for affecting the number of vertebrae in swine. Wild boars, which uniformly have 19 vertebrae, have the wild type allele while multi-vertebrae European commercial pigs have the mutated allele. Our aim was to confirm the factor of the miniaturization. Materials and methods We examined vertebrae number and NR6A1 polymorphism in the Microminipig and three domestic breeds that vary in body size. Results The Microminipig had 19 or less vertebrae and a wild type NR6A1 genotype. Three domestic breeds had more than 21 vertebrae while the largest vertebrae number was observed in multi-vertebrae-fixed Large White. Heterozygous genotypes were observed in the middle-sized indigenous pig while homozygous NR6A1 mutations were observed in European commercial breeds. Conclusion NR6A1 could be a useful index for both miniaturizing and increasing pig body size.

Background/Aim: Canine mammary gland tumors (MGTs), as a potential model of human breast cancer, have a well-defined histological classification system. MicroRNA (miRNA) expression is a key part of the molecular signatures of both MGTs and human breast cancer, although the signatures alone do not yet provide a sufficient basis for definitive diagnosis. In this study, we investigated the association between miRNA expression patterns and histological classification. Materials and Methods: Mammary gland tissue was collected from healthy dogs (n=7) and dog patients (n=80). Further samples (n=5) were obtained from established MGT cell lines. We targeted miRNAs differentially expressed in metastatic tumor tissue versus non-metastatic and normal tissue. A subset of samples was analyzed using small RNA next generation sequencing (NGS) with subsequent qPCR. Results: Six differentially expressed miRNAs were selected from the NGS analysis and submitted for large-scale qPCR. The large-scale qPCR analysis revealed greater alternations in miRNA expression. Large-scale analysis, based on 79 samples, revealed a hierarchical clustering based on selected miRNAs that did not strikingly match the histopathological subtype classification. Conclusion: We successfully investigated the large-scale miRNA expression pattern in canine MGT and provided the whole miRNA expression. The selected miRNA demonstrated that there is no straightforward mapping between molecular signatures and histological classification of canine MGTs at the miRNA level.

With the development of automotive power electronics and high-power integrated circuits, ribbon bonding is currently in the spotlight for its superior properties to those of traditional heavy wire bonding. In this article, innovative ribbon materials made of Ag and Ag–4Pd are introduced. The ultrasonic bonding of Ag and Ag-alloy ribbons on direct bonded copper (DBC) substrates metallized with Ni/Pd/Au films was evaluated as replacements for Al and Cu ribbons. A continuous bonding interface with satisfactory pull strength can be obtained from substrates metallized with Pd and Au films due to their similar metallurgical properties and softer surface conditions. The footprint study of bond residuals after pull tests correlated with the failure codes and bond strengths of the modules. The reliability of Ag and Ag–4Pd ribbons with regard to pull strength after high-temperature storage tests (HTSTs) at 150 °C for 1000 h was slightly increased, and the bond interface remained unchanged. The results showed that Ag and Ag-alloy ribbons made specifically for power electronics are feasible and can be an attractive alternative to aluminum ribbons.

The precipitation-hardenable aluminum alloy 6061 (AA 6061) is favored for aerospace components and automotive parts. However, the tenacious oxide layer on the surface greatly limits the quality and applicability of joining AA 6061. In this study, the joining method of solid-state diffusion bonding was implemented for AA 6061 plates, and the effects of post-weld heat treatment (PWHT) on the joint interface were investigated. The bonding temperatures were within the range of 500–530 °C, and the time periods varied from 30 to 240 min under a static pressure of 5 MPa in a vacuum. The diffusion bonded specimens were subjected to T4- and T6-PWHT to improve the bonding quality. The interfacial microstructure of the joints was analyzed by scanning electron microscopy, and the mechanical properties were evaluated with shear tests. The experimental results showed that the shear strength of the diffusion bonded joint could reach around 71.2 MPa, which was highly dependent on bonding temperature and holding time, and T6-PWHT further enhanced it to over 100 MPa. The effects of PWHT on the diffusion bonded AA 6061 joint were investigated, and the fractography on the sheared surfaces indicated that PWHT-T6 played an important role in enhancing joint strength, which was consistent with the measured shear strength. The sequential PWHT for AA 6061 after diffusion bonding was proven to be feasible for bonding of AA 6061 parts, and the joint strength was sufficient for industrial needs.

The expression levels of circulating microRNAs (miRNAs) can be affected by disease. The miRNA released from cells within exosomes can act as a remote communication tool and can participate in inflammatory response regulation. Therefore, circulating miRNA has the potential to be an indicator of local disease. The objective of this study was to investigate the serum level of bovine mastitis-related miRNAs. We found that miR-16 expression in serum was affected by hemolysis. The expression levels of miR-21 in serum were increased significantly in cows with mastitis compared with unaffected controls; however, the expression levels of miR-146a, miR-155, miR-222 and miR-383 in cows with mastitis were unchanged. We further verified the upregulation of miR-21 in the serum of cows with mastitis using a digital PCR system. Although the sensitivity and specificity of miR-21 in the serum to detect bovine mastitis was inferior to miRNA biomarkers in the milk, the significant increase of miR-21 in serum may reflect the impact of local inflammation on the systemic reaction.

Helicobacter pylori neutrophil-activating protein (HP-NAP), a major virulence factor of H. pylori, plays a role in bacterial protection and host inflammation. HP-NAP activates a variety of innate immune cells, including neutrophils, monocytes, and mast cells, to induce their pro-oxidant and pro-inflammatory activities. This protein also induces T-helper type 1 (Th1) immune response and cytotoxic T lymphocyte (CTL) activity, supporting that HP-NAP is able to promote gastric inflammation by activation of adaptive immune responses. Thus, HP-NAP is a potential therapeutic target for the treatment of H. pylori-induced gastric inflammation. The inflammatory responses triggered by HP-NAP are mediated by a PTX-sensitive G protein-coupled receptor and Toll-like receptor 2. Drugs designed to block the interactions between HP-NAP and its receptors could alleviate the inflammation in gastric mucosa caused by H. pylori infection. In addition, HP-NAP acts as a promising therapeutic agent for vaccine development, allergy treatment, and cancer immunotherapy. The high antigenicity of HP-NAP makes this protein a component of vaccines against H. pylori infection. Due to its immunomodulatory activity to stimulate the Th1-inducing ability of dendritic cells, enhance Th1 immune response and CTL activity, and suppress Th2-mediated allergic responses, HP-NAP could also act as an adjuvant in vaccines, a drug candidate against allergic diseases, and an immunotherapeutic agent for cancer. This review highlights the role of HP-NAP in the pathogenesis of H. pylori and the potential for this protein to be a therapeutic target in the treatment of H. pylori infection and therapeutic agents against H. pylori-associated diseases, allergies, and cancer.

Mastitis is a common inflammatory infectious disease in dairy cows. To understand the microRNA (miRNA) expression profile changes during bovine mastitis, we undertook a genome-wide miRNA study of normal milk and milk that tested positive on the California mastitis test for bovine mastitis (CMT+). Twenty-five miRNAs were differentially expressed (23 miRNAs upregulated and two downregulated) during bovine mastitis relative to their expression in normal milk. Upregulated mature miR-1246 probably derived from a U2 small nuclear RNA rather than an miR-1246 precursor. The significantly upregulated miRNA precursors and RNU2 were significantly enriched on bovine chromosome 19, which is homologous to human chromosome 17. A gene ontology analysis of the putative mRNA targets of the significantly upregulated miRNAs showed that these miRNAs were involved in binding target mRNA transcripts and regulating target gene expression, and a Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the upregulated miRNAs were predominantly related to cancer and immune system pathways. Three novel miRNAs were associated with bovine mastitis and were relatively highly expressed in milk. We confirmed that one of the novel mastitis-related miRNAs was significantly upregulated using a digital PCR system. The differentially expressed miRNAs were involved in human cancers, infections, and immune-related diseases. The genome-wide analysis of miRNA profiles in this study provides insight into bovine mastitis and inflammatory diseases. DATABASES: The miRNAseq generated for this study can be found in the Sequence Read Archive (SRA) under BioProject Number PRJNA421075 and SRA Study Number SRP126134 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA421075).

Dogs have been considered as an excellent immunocompetent model for human melanoma due to the same tumor location and the common clinical and pathological features with human melanoma. However, the differences in the melanoma transcriptome between the two species have not been yet fully determined. Considering the role of oncogenes in melanoma development, in this study, we first characterized the transcriptome in canine oral melanoma and then compared the transcriptome with that of human melanoma. The global transcriptome from 8 canine oral melanoma samples and 3 healthy oral tissues were compared by RNA‑Seq followed by RT‑qPCR validation. The results revealed 2,555 annotated differentially expressed genes, as well as 364 novel differentially expressed genes. Dog chromosomes 1 and 9 were enriched with downregulated and upregulated genes, respectively. Along with 10 significant transcription site binding motifs; the NF‑κB and ATF1 binding motifs were the most significant and 4 significant unknown motifs were indentified among the upregulated differentially expressed genes. Moreover, it was found that canine oral melanoma shared >80% significant oncogenes (upregulated genes) with human melanoma, and JAK‑STAT was the most common significant pathway between the species. The results identified a 429 gene signature in melanoma, which was up‑regulated in both species; these genes may be good candidates for therapeutic development. Furthermore, this study demonstrates that as regards oncogene expression, human melanoma contains an oncogene group that bears similarities with dog oral melanoma, which supports the use of dogs as a model for the development of novel therapeutics and experimental trials before human application.

In this study, different grain growth paths after aging at various temperatures for 1 h were observed in Ag nanotwinned thin films with and without substrate bias voltage, which led to large differences in thermal stability. As-deposited Ag nanotwinned thin films with and without substrate bias voltage were characterized by FIB, EBSD, and TEM, which revealed thinner equiaxial fine-grained regions, higher amounts of (111)-oriented grains and denser nanotwin stacking perpendicular to the growth direction of columnar grains in thin films with -150 V substrate bias voltage. Due to the better lattice arrangement and densification of the crystal structure due to substrate bias voltage, the microstructures remained almost unchanged, except for a little equiaxial grain growth, even after aging at 450 °C for 1 h. However, in the Ag nanotwinned thin film without substrate bias voltage, severe abnormal grain growth (AGG) occurred after aging at only 250 °C for 1 h. Better understanding of the differences in thermal stability in nanotwinned thin films is provided in this study, and the findings will be beneficial for experimental design for further applications.

Canine mammary gland tumors are very common and represent a potential model of human breast cancer, and microRNA (miRNAs) are promising biomarkers and therapeutic targets for these tumors. Accordingly, we aimed to identify miRNAs differentially expressed in canine mammary gland tumors using next generation sequencing (NGS), with subsequent confirmatory qPCR and target gene analyses. Mammary gland tissue was collected from healthy dogs (n=7) and dogs with suspected tumors (n=80). A subset of samples was analyzed with NGS to identify differentially expressed miRNAs with CLC Genome Workbench. Normal (n=10), tumor-adjacent (n=6), and tumor-bearing (n=76) mammary gland tissue samples were analyzed for the identified miRNAs using qPCR. An in silico analysis (TargetScan) was performed to predict the miRNAs' target genes using gene ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database (DAVID). We identified four miRNAs (cfa-miR-1-3p, cfa-miR-133a-3p, cfa-miR-133b-3p, and cfa-miR-133c-3p) as down regulated in canine mammary gland tumor tissues relative to normal and tumor adjacent tissues. KEGG analysis revealed the potential target genes of cfa-miR-1-3p are related to the Rap1 signaling pathway, adherens junction, and Ras signaling pathway, and those of the miR-133 family are related to the TGF-beta signaling pathway, synaptic vesicle cycle, and sphingolipid signaling pathway. In combination, these target genes are related to the regulation of transcription and DNA binding transcription (GO analysis), and the Hippo signaling pathway, adherens junction, and endocytosis (KEGG analysis). Accordingly, we suggest these four miRNAs are promising potential biomarker candidates for canine mammary gland tumors warranting further investigation.

MicroRNAs (miRNAs) can rapidly respond to cellular stresses, such as hypoxia. This immediate miRNA response regulates numerous genes and influences multiple signaling pathways. Therefore, identifying hypoxia-regulated miRNAs (HRMs) is important in canine oral melanoma (COM) to investigate their clinical significance. The hypoxic and normoxic miRNA profiles of two COM cell lines were investigated by next generation sequencing. HRMs were identified by comparing miRNA expression profiles in these cell lines with that in COM tissue. The HRM profile was different between cell lines of primary and metastatic origin, except for miR-301a and miR-8884. The time course of miRNA expression determined by qRT-PCR, especially for miR-210 and miR-301a, showed that metastatic cells are more resistant to hypoxia than primary cells. Analysis of an experimentally validated human miRNA target database revealed that miR-21 and miR-301a control a complex gene regulatory network in response to hypoxia, which includes pathways of well-known oncogenes, such as VEGF, PTEN, and TGFBR2. In conclusions, we revealed the HRM of COM. Moreover, our study shows the difference in regulation and response of hypoxic miRNAs between primary and metastatic originated melanoma cells.

We examined whether multidrug resistant (MDR) canine lymphoma increases gene expression for platelet-derived growth factor receptor α (PDGFRα), vascular endothelial growth factor receptor 2 (VEGFR2), and c-KIT, and whether toceranib phosphate (TOC) has potential as a treatment for MDR canine lymphoma. The clinical data showed that PDGFRα expression was higher in canine subjects with MDR T-cell lymphoma than in those with untreated T-cell lymphoma, and that c-KIT expression was greater in subjects with T-cell lymphoma than in those with B-cell lymphoma. TOC monotherapy was well tolerated without serious adverse effects, and two of the five subjects that received TOC exhibited partial responses. The data presented here could contribute to the assessment of TOC-based therapy for dogs with MDR or T-cell lymphoma.

Our aim was to identify a suitable microRNA housekeeping gene for real-time PCR analysis of bovine mastitis-related microRNA in milk. We identified , , and as housekeeping gene candidates on the basis of previous Solexa sequencing results. Threshold cycle (CT) values for , , and did not differ between milk from control cows and milk from mastitis-affected cows. NormFinder software identified as the most stable single housekeeping gene. We evaluated the suitability of the housekeeping gene candidates by using them to assess expression levels of the inflammation-related gene . Regardless of the housekeeping gene candidates used for normalization, relative expression levels of were significantly higher in mastitis-affected samples than in control samples. However, of all the housekeeping genes and gene combinations investigated, normalization with alone generated the difference in relative expression between mastitis-affected and control samples with the highest significance. These results suggest that is suitable for use as a housekeeping gene for analysis of bovine mastitis-related microRNA in milk.

MicroRNAs (miRNAs) dysregulation contribute the cancer pathogenesis. However, the miRNA profile of canine oral melanoma (COM), one of the frequent malignant melanoma in dogs is still unrevealed. The aim of this study is to reveal the miRNA profile in canine oral melanoma. MiRNAs profile of oral tissues from normal healthy dogs and COM patients were compared by next-generation sequencing. Along with tumour suppressor miRNAs, we report 30 oncogenic miRNAs in COM. The expressions of miRNAs were further confirmed by quantitative real-time PCR (qPCR). Pathway analysis showed that deregulated miRNAs impact on cancer and signalling pathways. Three oncogenic miRNAs targets (miR-450b, 301a, and 223) from human study also were down-regulated in COM and had a significant negative correlation with their respective miRNA. Furthermore, we found that miR-450b expression is higher in metastatic cells and regulated MMP9 expression through a PAX9-BMP4-MMP9 axis. In silico analysis indicated that miR-126, miR-20b, and miR-106a regulated the highest numbers of differentially expressed transcription factors with respect to human melanoma. Chromosomal enrichment analysis revealed the X chromosome was enriched with oncogenic miRNAs. We comprehensively analyzed the miRNA&rsquo, s profile in COM which will be a useful resource for developing therapeutic interventions in both species.

Among small non-coding RNAs (sncRNAs/sRNAs), the functional regulation of microRNAs (miRNAs) has been studied in canine oral melanoma (COM). However, the expression level of other sncRNAs, like small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs), transfer RNA-derived fragments (tRFs) and PIWI-interacting RNAs (piRNAs), in COM is unknown. The aim of this study was to investigate sncRNAs other than miRNAs in COM from our small RNA sequencing project (PRJNA516252). We found that several snRNAs and piRNAs were upregulated, whereas tRFs and snoRNAs were downregulated in COM. Upregulation of U1 snRNA and piR-972, and downregulation of tRNA-ser (1) and snoRA24 was confirmed in dog melanoma tissue and cell lines by quantitative reverse transcription PCR. Consistently, the expression of tRNA-ser (1) and snoRA24 in plasma of COM cases was also decreased. Finally, we found a similar expression trend of U1 and snoRA24 in the human cutaneous melanoma cell line, MEWO, compared with human epidermal melanocyte cells (HEMa-Lp). In our study, snRNA, snoRNA, tRFs and piRNA were dysregulated during melanoma progression. Moreover, the melanoma-associated expression of U1 and snoRA24 was similar in human and dog melanoma.

In this study, low-temperature Ag Ag direct bonding was achieved at 150–250 °C in 10–60 min by using high (111)-preferred orientation films with densely-packed nanotwins fabricated by magnetron sputtering process. The focused ion beam (FIB) and transmission electron microscopy (TEM) results showed great bonding interfaces with almost no voids. The top-view electron backscattered diffraction (EBSD) results indicated that the grains on the surface before bonding were almost 100% (98.4%) (111)-preferred orientation grains, which provided a rapid path for diffusion. High thermal stability was observed, for the twin thickness remained unchanged after bonding at various temperatures. The bonding technique shows great potential for application in MEMS, optoelectronics, transducers, heat-sensitive components and 3D IC interconnections.

In this study, the microstructural evolution of Ag-4Pd ribbon under various annealing conditions was investigated via electron backscatter diffraction (EBSD) technique. The as-manufactured Ag-4Pd ribbon, with an initial grain size of 3.66 µm and twin density of 53.1%, was held under different annealing treatment conditions of 623–1073 K for time periods of 0.5–100 h. The grain size distribution showed that after prolonged annealing treatment, the distribution deviated from the normal distribution, indicating that abnormal grain growth occurred. The grain growth time exponent (n) was calculated to be 0.35 and decreased with annealing temperature. The activation energy obtained from the growth rate of the grains was found to be 1.46 eV, indicating the dominance of grain boundary diffusion. The deviation of the n value and activation energy from those of pure silver could be attributed to the alloying Pd content and the presence of abundant twin boundaries within the microstructure of the Ag-4Pd ribbon, which was confirmed by EBSD results. The mechanical behavior of this material is also discussed, providing insight into a theoretical basis for application in a high-power IC module.

Inhibiting aberrantly upregulated microRNAs (miR/miRNAs) has emerged as a novel focus for therapeutic intervention in human melanoma. Thus, identifying upregulated miRNAs is essential for identifying additional melanoma-associated therapeutic targets. In the present study, microarray-based miRNA profiling of canine malignant melanoma (CMM) tissue obtained from the oral cavity was performed and differential expression was confirmed by a reverse transcription-quantitative polymerase chain reaction (RT-qPCR). An analysis of the microarray data revealed 17 dysregulated miRNAs; 5 were upregulated and 12 were downregulated. RT-qPCR analysis was performed for 2 upregulated (miR-204 and miR-383), 3 downregulated (miR-122, miR-143 and miR-205) and 6 additional oncogenic miRNAs (oncomiRs; miR-16, miR-21, miR-29b, miR-92a, miR-125b and miR-222). The expression levels of seven of the miRNAs, miR-16, miR-21, miR-29b, miR-122, miR-125b, miR-204 and miR-383 were significantly upregulated; however, the expression of miR-205 was downregulated in CMM tissues compared with normal oral tissues. The microarray and RT-qPCR analyses validated the upregulation of two potential oncomiRs miR-204 and miR-383. The present study additionally constructed a protein interaction network and a miRNA-target regulatory interaction network using STRING and Cytoscape. In the proposed network, cyclin dependent kinase 2 was a target for miR-383, sirtuin 1 and tumor protein p53 were targets for miR-204 and ATR serine/threonine kinase was a target for both. It was concluded that miR-383 and miR-204 were potential oncomiRs that may be involved in regulating melanoma development by evading DNA repair and apoptosis.

Canine hepatocellular carcinoma (HCC) is the most common primary hepatic tumour in dogs. MicroRNA (miRNA) dysregulation has been reported in human HCC and shown to have diagnostic and prognostic value; however, there are no data on miRNA expression in canine HCC. The aim of the present study was to investigate differentially expressed miRNAs in canine HCC. Analysis of miRNA expression in canine HCC tissues and cell lines by quantitative reverse transcription PCR showed that miR-1, miR-122, let-7a, and let-7g were downregulated, whereas miR-10b and miR-21 were upregulated in canine HCC. MET is one of the target genes of miR-1. MET was upregulated in canine HCC at the gene and protein levels, and a significant correlation between the concomitant downregulation of miR-1 and upregulation of MET was observed. Fast/intermediate-proliferating canine HCC cell lines had higher MET gene and protein expression levels than the slow-proliferating cell line. These findings suggest that miRNAs are differentially expressed in canine HCC, and that the miR-1/MET pathway may be associated with canine HCC cell proliferation.

MicroRNA (miRNA) in tissue and liquid samples have been shown to be associated with many diseases including inflammation. We aimed to identify inflammation-related miRNA expression level in the bovine mastitis milk. Expression level of inflammation-related miRNA in milk from mastitis-affected and normal cows was analyzed using qPCR. We found that expression level of miR-21, miR-146a, miR-155, miR-222, and miR-383 was significantly upregulated in California mastitis test positive (CMT+) milk. We further analyzed these miRNA using a chip-based QuantStudio Digital PCR System. The digital PCR results correlated with those of qPCR, demonstrating upregulation of miR-21, miR-146a, miR-155, miR-222, and miR-383 in CMT+ milk. In conclusion, we identified miRNA that are upregulated in CMT+ milk. These miRNA exhibited sensitivity and specificity greater than 80% for differentiating between CMT+ milk and normal milk. Our findings suggest that inflammation-related miRNA expression level in the bovine milk was affected by mastitis, and miRNA in milk have potential for use as biomarkers of bovine mastitis.

Many chemicals used in modern printing processes are either toxic or difficult to decompose, which results in the production of complicated and refractory printing wastewater. In this study, an electrocatalytic technology with different catalytic electrodes was employed to treat a real printing wastewater, and the production rates of hydroxyl radicals were determined. The results indicate that under a voltage gradient of 11 V cm −1 , the production concentration of hydroxyl radicals by various electrodes followed a decreasing order of TiO 2 > DSA (dimensional sustainable anode with IrO 2 ) > graphite, with the values of 8.21 × 10 −3 , 5.24 × 10 −3 , and 0.86 × 10 −3 M, respectively. A lower wastewater conductivity could lead to a greater electric voltage thus contributing to a higher removal efficiency of TOC and chroma. At a current density of 50 mA cm −2 and using one pair of electrodes (IrO 2 + stainless steel), the TOC and chroma removal efficiencies reached 71% and 53% after 60 min treatment. Under the same operation conditions but using two pairs of electrodes, the removal efficiencies of TOC and chroma were increased to 75% and 82%, respectively. The removal efficiencies of TOC and chroma could be further raised to 90% and 92% if the electrocatalytic effluent was polished by powder activated carbon absorption.

We tested the hypotheses that hypoxic stimulation enhances growth potentials of canine lymphoma cells by activating hypoxia-inducible factor 1α (HIF-1α), and that the hypoxia-activated prodrug (TH-302) inhibits growth potentials in the cells. We investigated how hypoxic culture affects the growth rate, chemoresistance, and invasiveness of canine lymphoma cells and doxorubicin (DOX)-resistant lymphoma cells, and influences of TH-302 on survival rate of the cells under hypoxic conditions. Our results demonstrated that hypoxic culture upregulated the expression of HIF-1α and its target genes, including ATP-binding cassette transporter B1 (ABCB1), ATP-binding cassette transporter G2 (ABCG2), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and survivin, and enhanced the growth rate, DOX resistance, and invasiveness of the cells. Additionally, TH-302 decreased the survival rate of the cells under hypoxic condition. Our studies suggest that hypoxic stimulation may advance the tumorigenicity of canine lymphoma cells, favoring malignant transformation. Therefore, the data presented may contribute to the development of TH-302-based hypoxia-targeting therapies for canine lymphoma.