Dent corn Andisol at the Hokkaido University Shizunai Livestock Experimental Farm actively emits nitrous oxide (N2O). In order to screen for culturable and active N2O emitters with high N2O emission potential, soft gel medium containing excess KNO3 was inoculated with soil suspensions from farm soil samples collected at different land managements. Dominant bacterial colonies were searched for among 20 of the actively N2O-emitting cultures from post-harvest soil and 19 from pre-tilled soil, and all isolates were subjected to the culture-based N2O emission assay. Ten active N2O-emitting bacteria, four from post-harvest soil and six from pre-tilled soil, out of 156 isolates were identified as genus Pseudomonas by 16S rRNA gene sequencing. These N2O emitters showed clear responses to NO3(-) within a neutral pH range (5.5-6.7), and accelerated N2O production with 1.5-15 mM sucrose supplementation, suggesting the production of N2O during the denitrification process. However, the negative responses of 6 active N2O emitters, 3 from post-harvest soil and 3 from pre-tilled soil, out of the 10 isolates in the acetylene-blocking assay suggest that these 6 N2O emitters are incomplete denitrifiers that have lost their N2O reductase (N2OR) activity. Although the PCR assay for the denitrification-associated genes, narG and nirK/S, was positive in all 10 Pseudomonas isolates, those negative in the acetylene-blocking assay were nosZ-negative. Therefore, these results imply that the high N2O emission potential of dent corn Andisol is partly attributed to saprophytic, nosZ gene-missing pseudomonad denitrifiers.

Japanese encephalitis virus (JEV) consists of five genotypes (GI-V). Phylogenetic characterization of 16 JEV strains isolated from the 'USSR', Japan and Korea during the 1930-1970s revealed that 15 strains fell into GIII, confirming that GIII was the predominant genotype of JEV in Japan and Korea between 1935 (isolation of the prototype strain; a GIII virus) and the 1990s (when GI supplanted GIII). One of the Korean isolates fell into GII, demonstrating that GII has been circulating for at least 19 years longer than previously thought. Formerly, GII was associated with endemic disease and this genotype had never been isolated north of Southern Thailand. Additionally, the northern border of GIII prevalence was extended from Japan to the 'USSR'.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Corresponding Author with the agreement of the editor. The authors used DMSO (dimethyl sulfoxide) to dissolve tanshinone IIA in this experiment, but even after dilution, DMSO also can induce toxicity of PC12 cells, which also can affect the result of the experiment. After discussion, the authors found that sulfotanshinone sodium injection can be used to replace tanshinone II A, which is both an aqueous solution and has been clinically proved to be an ideal substitute. Further, in error, the authors used 0μM /12.5μM /50μM /100μM /200μM H2O2 to stimulate oxidative injury as in figure 1A, but missed 25μM H2O2, which may also affect the experimental results.

Pacific oyster Crassostrea gigas, endemic to coastal Asia, has been translocated globally throughout the past century, resulting in self-sustaining introduced populations (naturalized). Oyster aquaculture industries in many parts of the world depend on commercially available seed (hatchery-farmed) or naturalized/wild oysters to move onto a farm (naturalized-farmed). It is therefore important to understand genetic variation among populations and farm types. Here, we genotype naturalized/wild populations from France, Japan, China, and most extensively in coastal British Columbia, Canada. We also genotype cultured populations from throughout the Northern Hemisphere to compare with naturalized populations. In total, 16,942 markers were identified using double-digest RAD-sequencing in 182 naturalized, 112 hatchery-farmed, and 72 naturalized-farmed oysters (n = 366). Consistent with previous studies, very low genetic differentiation was observed around Vancouver Island (mean F ST = 0.0019) and low differentiation between countries in the Japan-Canada-France historical translocation lineage (France-Canada F ST = 0.0024; Japan-Canada F ST = 0.0060). Chinese populations were more differentiated (China-Japan F ST = 0.0241). Hatchery-propagated populations had higher interindividual relatedness suggesting family structure. Within-population inbreeding was not detected on farms, but nucleotide diversity and polymorphism rate were lower in one farm population. Moving oysters from nature onto farms did not result in strong within-generation selection. Private alleles at substantial frequency were identified in several hatchery populations grown in BC, suggesting nonlocal origins. Tests of selection identified outlier loci consistent with selective differences associated with domestication, in some cases consistently identified in multiple farms. Top outlier candidates were nearby genes involved in calcium signaling and calmodulin activity. Implications of potential introgression from hatchery-farmed oysters depend on whether naturalized populations are valued as a locally adapted resource or as an introduced, invasive species. Given the value of the industry in BC and the challenges the industry faces (e.g., climate change, crop losses, biotic stressors), this remains an important question.

Recurring epidemics of kiwifruit (Actinidia spp.) bleeding canker disease are caused by Pseudomonas syringae pv. actinidiae (Psa). In order to strengthen understanding of population structure, phylogeography, and evolutionary dynamics, we isolated Pseudomonas from cultivated and wild kiwifruit across six provinces in China. Based on the analysis of 80 sequenced Psa genomes, we show that China is the origin of the pandemic lineage but that strain diversity in China is confined to just a single clade. In contrast, Korea and Japan harbor strains from multiple clades. Distinct independent transmission events marked introduction of the pandemic lineage into New Zealand, Chile, Europe, Korea, and Japan. Despite high similarity within the core genome and minimal impact of within-clade recombination, we observed extensive variation even within the single clade from which the global pandemic arose.

Metabolic syndrome can induce chronic renal injury in humans. In the present study, Bama minipigs were fed a high-fat/high-sucrose diet (HFHSD) for 23 months, which caused them to develop the pathological characteristics of metabolic syndrome, including obesity, hyperinsulinemia, and hyperlipidemia, and resulted in kidney tissue damage. In the HFHSD group, the ratio of the glomus areas to the glomerulus area and the glomerular density inside the renal cortex both decreased. Lipid deposition in the renal tubules was detected in the HFHSD group, and up-regulated expression levels of SREBP-1, FABP3 and LEPR promoted lipid deposition. The decreased levels of SOD, T-AOC and GSH-PX indicated that the antioxidant capacity of the renal tissues was diminished in the HFHSD group compared with MDA, which increased. The renal tissue in the HFHSD group exhibited clear signs of inflammation as well as significantly elevated expression of key genes associated with inflammation, including tumor necrosis factor-α (TNF-α) and macrophage migration inhibitory factor (MIF), compared with the control group. The tubular epithelial cells in the HFHSD group displayed significantly greater numbers of apoptotic cells, and the expression of proliferating cell nuclear antigen (PCNA) in the renal tubules decreased. Caspase-3 expression increased significantly, and the transcription factor nuclear factor κB (NF-κB) was activated and translocated into the nucleus. In conclusion, long-term HFHSDs cause metabolic syndrome and chronic renal tissue injury in Bama minipigs. These findings provide a foundation for further studies investigating metabolic syndrome and nephropathy.

Human epidermal growth factor receptor 3 (HER3) is broadly expressed in breast cancer; high expression is associated with an adverse prognosis. Patritumab deruxtecan (HER3-DXd) is an investigational HER3-targeted antibody-drug conjugate that is being evaluated as a novel treatment in HER3-expressing advanced breast cancer in the U31402-A-J101 study.

Burkholderia heleia PAK1-2 is a potent biocontrol agent isolated from rice rhizosphere, as it prevents bacterial rice seedling blight disease caused by Burkholderia plantarii. Here, we isolated a non-antibacterial metabolite from the culture fluid of B. heleia PAK1-2 that was able to suppress B. plantarii virulence and subsequently identified as indole-3-acetic acid (IAA). IAA suppressed the production of tropolone in B. plantarii in a dose-dependent manner without any antibacterial and quorum quenching activity, suggesting that IAA inhibited steps of tropolone biosynthesis. Consistent with this, supplementing cultures of B. plantarii with either L-[ring-(2)H5]phenylalanine or [ring-(2)H2~5]phenylacetic acid revealed that phenylacetic acid (PAA), which is the dominant metabolite during the early growth stage, is a direct precursor of tropolone. Exposure of B. plantarii to IAA suppressed production of both PAA and tropolone. These data particularly showed that IAA produced by B. heleia PAK1-2 disrupts tropolone production during bioconversion of PAA to tropolone via the ring-rearrangement on the phenyl group of the precursor to attenuate the virulence of B. plantarii. B. heleia PAK1-2 is thus likely a microbial community coordinating bacterium in rhizosphere ecosystems, which never eliminates phytopathogens but only represses production of phytotoxins or bacteriocidal substances.

In addition to potentially progressing to either cirrhosis or hepatocellular carcinoma, non-alcoholic steatohepatitis (NASH) is currently the leading indication for liver transplantation. Nintedanib has been clinically used to treat idiopathic pulmonary fibrosis for many years, but its effects in an animal model of NASH have not been tested. The purpose of this study was to evaluate the effects of nintendanib on NASH in choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD)-fed mice.

Physiome.jp (http://physiome.jp) is a portal site inaugurated in 2007 to support model-based research in physiome and systems biology. At Physiome.jp, several tools and databases are available to support construction of physiological, multi-hierarchical, large-scale models. There are three databases in Physiome.jp, housing mathematical models, morphological data, and time-series data. In late 2013, the site was fully renovated, and in May 2015, new functions were implemented to provide information infrastructure to support collaborative activities for developing models and performing simulations within the database framework. This article describes updates to the databases implemented since 2013, including cooperation among the three databases, interactive model browsing, user management, version management of models, management of parameter sets, and interoperability with applications.

Activation of ribosomal RNA (rRNA) synthesis is pivotal during cell growth and proliferation, but its aberrant upregulation may promote tumorigenesis. Here, we demonstrate that the candidate oncoprotein, LYAR, enhances ribosomal DNA (rDNA) transcription. Our data reveal that LYAR binds the histone-associated protein BRD2 without involvement of acetyl-lysine-binding bromodomains and recruits BRD2 to the rDNA promoter and transcribed regions via association with upstream binding factor. We show that BRD2 is required for the recruitment of the MYST-type acetyltransferase KAT7 to rDNA loci, resulting in enhanced local acetylation of histone H4. In addition, LYAR binds a complex of BRD4 and KAT7, which is then recruited to rDNA independently of the BRD2-KAT7 complex to accelerate the local acetylation of both H4 and H3. BRD2 also helps recruit BRD4 to rDNA. By contrast, LYAR has no effect on rDNA methylation or the binding of RNA polymerase I subunits to rDNA. These data suggest that LYAR promotes the association of the BRD2-KAT7 and BRD4-KAT7 complexes with transcription-competent rDNA loci but not to transcriptionally silent rDNA loci, thereby increasing rRNA synthesis by altering the local acetylation status of histone H3 and H4.

Hypericum perforatum L. has been widely used as a natural antidepressant. However, it is unknown whether it is effective in treating infection-induced neuropsychiatric disorders.

Crop performance is seriously affected by high salt concentrations in soils. To develop improved seed pre-sowing treatment technologies, it is crucial to improve the salt tolerance of seed germination. Here, we isolated and identified the strain Bacillus sp. MGW9 and developed the seed biostimulant MGW9. The effects of seed biopriming with the seed biostimulant MGW9 in maize (Zea mays L.) under saline conditions were studied. The results show that the strain Bacillus sp. MGW9 has characteristics such as salt tolerance, nitrogen fixation, phosphorus dissolution, and indole-3-acetic acid production. Seed biopriming with the seed biostimulant MGW9 enhanced the performance of maize during seed germination under salinity stress, improving the germination energy, germination percentage, shoot/seedling length, primary root length, shoot/seedling fresh weight, shoot/seedling dry weight, root fresh weight and root dry weight. Seed biostimulant MGW9 biopriming also alleviated the salinity damage to maize by improving the relative water content, chlorophyll content, proline content, soluble sugar content, root activity, and activities of superoxide dismutase, catalase, peroxidase and ascorbate peroxidase, while decreasing the malondialdehyde content. In particular, the field seedling emergence of maize seeds in saline-alkali soil can be improved by biopriming with the seed biostimulant MGW9. Therefore, maize seed biopriming with the seed biostimulant MGW9 could be an effective approach to overcoming the inhibitory effects of salinity stress and promoting seed germination and seedling growth.

Hepatocarcinoma is a type of high-grade malignant carcinoma identified worldwide. Its rapid development and late diagnosis prevents effective tumor resection in the majority of patients, and therefore recent studies have targeted metabolic signaling pathways and the tumor microenvironment for potential treatments. To investigate whether endocan may be a gene target for hepatocarcinoma treatment, the present study employed the following measures: MTT and Transwell assays, flow cytometry, western blotting and an mRFP-GFP-LC3 double fluorescence system. Following endocan gene silencing, cell proliferation was significantly inhibited and the number of invasive cells in the endocan siRNA-treated group was reduced compared with the control-siRNA treated-group. Furthermore, the apoptosis rate was 15% and autophagy was detected in the endocan short interfering (si)RNA-treated group compared with the control-siRNA treated-group. Using western blotting to detect NF-κB expression in the nucleus, the NF-κB expression was identified to be significantly reduced in the siRNA-treated group compared with the control groups. Endocan gene silencing inhibited hepatocarcinoma cell viability and invasion, whilst inducing apoptosis and autophagy. The results of the present study suggest that the effect of endocan gene silencing on cell survival was mediated via the NF-κB signaling pathway.

Adiponectin (APN) is an important anti‑atherogenic adipocytokine. The aim of the present study was to investigate the role of adiponectin in atherosclerotic plaque formation and clarify its mechanisms. An atherosclerosis model was induced by in vivo perivascular constrictive silica collar placement on the left common carotid arteries in male apolipoprotein E‑deficient (ApoE‑/‑) mice. All of the mice were fed a high‑fat diet, and divided into phosphate‑buffered saline, adenovirus (Ad)‑β‑galactosidase and Ad‑APN treatment groups. Compared with treatment of Ad‑β‑gal or PBS, Ad‑APN treatment markedly reduced inducible nitric oxide synthase (iNOS) protein expression, decreased in nitric oxide/superoxide production, blocked peroxynitrite formation and reversed the progression of atherosclerotic lesions. Adiponectin may be a natural molecule that reduces atherosclerosis by inhibiting iNOS and consequently diminishing oxidative/nitrative stress.

Down syndrome (DS) is caused by the trisomy of chromosome 21. Among the many disabilities found in individuals with DS is an increased risk of early-onset Alzheimer's disease (AD). Although higher oxidative stress and an upregulation of amyloid β (Aβ) peptides from an extra copy of the APP gene are attributed to the AD susceptibility, the relationship between the two factors is unclear. To address this issue, we established an in vitro cellular model using neurons differentiated from DS patient-derived induced pluripotent stem cells (iPSCs) and isogenic euploid iPSCs. Neurons differentiated from DS patient-derived iPSCs secreted more Aβ compared to those differentiated from the euploid iPSCs. Treatment of the neurons with an antioxidant, N-acetylcysteine, significantly suppressed the Aβ secretion. These findings suggest that oxidative stress has an important role in controlling the Aβ level in neurons differentiated from DS patient-derived iPSCs and that N-acetylcysteine can be a potential therapeutic option to ameliorate the Aβ secretion.

Loganin, an iridoid glycoside, is one of the quality control indexes of Cornus officinalis Sieb. et Zucc. Increasing evidence emphasize the important role of inflammation in the pathology of depression, which links depression with other chronic diseases. Loganin prevents inflammatory response in multiple diseases and reverses depressive-like behaviors. However, the mechanisms underlying antidepressant-like effects of loganin for the treatment of inflammation-associated depression are not utterly understood.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by chronic synovitis, bone erosion, and bone loss. Erzhi Pill (EZP), a classic Chinese patent medicine, is often used to treat osteoporosis and shows a capacity for bone metabolism regulation. Methotrexate (MTX), an essential drug for RA treatment, has been reported to inhibit generalized bone loss in RA patients. However, the combined therapeutic effects and mechanism of EZP and MTX in RA have not been fully elucidated. The aim of this study was to investigate the synergistic effect of EZP and MTX on RA and to explore the underlying mechanism through network pharmacological prediction and experimental verification. Chemical compounds of EZP, human target proteins of EZP and MTX, and RA-related human genes were identified in the Encyclopedia of Traditional Chinese Medicine database, PubChem database, and NCBI database, respectively. The molecular network of EZP and MTX in RA was generated and analyzed with Ingenuity Pathway Analysis software according to the datasets. Then, MTX monotherapy, EZP monotherapy, and combined MTX and EZP therapy were administered to collagen-induced arthritis rats, followed by assessment of pathological score, bone damage, bone alkaline phosphatases (BALP), and tartrate-resistant acid phosphatase (TRACP), and of gene levels related to the Wnt1/LRP5/β-catenin pathway according to network pharmacological analysis. Finally, serum samples from MTX-, EZP- and MTX+EZP-treated rats were used to treat the rat osteoblast (OB)-like UMR-106 cell line to evaluate gene levels related to Wnt1/LRP5/β-catenin. Network pharmacological analysis showed that the Wnt/β-catenin signaling pathway was the top signaling pathway shared among MTX, EZP, and RA. The results from in vivo experiments indicated that EZP combined with MTX reduced arthritis severity, alleviated ankle bone damage, increased BALP and decreased TRACP serum levels, and regulated the mRNA expression of Wnt1, LRP5, β-catenin, Runx2, BALP, and BGP in the ankles. In vitro experiments showed that EZP combined with MTX could also improve the expression of genes related to the Wnt1/LRP5/β-catenin pathway. This study demonstrated that EZP in combination with MTX played a synergistic role in regulating OBs in RA, which was connected to the modulatory effect of EZP and MTX on the Wnt1/LRP5/β-catenin signaling pathway.

Strains of Monascus filamentous fungal species have been used to produce fermented foods in Asian countries, such as China, Japan, and The Korean Peninsula, for nearly 2,000 years. At present, their fermented products are widely used as food additives and nutraceutical supplements worldwide owing to their production of beneficial secondary metabolites. Heterotrimeric G-protein signaling pathways participate in regulating multiple biological processes in fungi. Previously, we identified three Monascus ruber M7 G-protein α subunits (Mga1-3) and demonstrated that Mga1 can regulate growth, reproduction and some secondary metabolites' production. Here, we systematically analyzed and compared the roles of mga1-3 by combining single- and double-gene(s) knockouts and their transcriptomic data. First, mga2 and mga3 knock-out mutants and pairwise combinations of mga1-3 deletion strains were generated. Then the changes in growth, development and the main secondary metabolites, Monascus pigments and citrinin, in these mutants were systematically compared with M. ruber M7. Moreover, RNA-Seq analyses of these mutants were performed. All three Gα subunits worked together to regulate biological processes in M. ruber M7, with Mga1 playing a major role, while Mga2 and Mga3 playing supplemental roles. According to the existing literatures which we can find, gene knock-out mutants of the pairwise combination of mga1-3 and their transcriptome analysis are first reported in this study. The current results have clearly demonstrated the functional division of Mga1-3 in M. ruber M7, and could provide a deeper understanding of the effects of different Gα subunits on growth, development and secondary metabolism in other filamentous fungi.

Single nucleotide polymorphisms (SNPs) are widely used in genetics and genomics research. The Pacific oyster (Crassostrea gigas) is an economically and ecologically important marine bivalve, and it possesses one of the highest levels of genomic DNA variation among animal species. Pacific oyster SNPs have been extensively investigated; however, the mechanisms by which these SNPs may be used in a high-throughput, transferable, and economical manner remain to be elucidated. Here, we constructed an oyster 190K SNP array using Affymetrix Axiom genotyping technology. We designed 190,420 SNPs on the chip; these SNPs were selected from 54 million SNPs identified through re-sequencing of 472 Pacific oysters collected in China, Japan, Korea, and Canada. Our genotyping results indicated that 133,984 (70.4%) SNPs were polymorphic and successfully converted on the chip. The SNPs were distributed evenly throughout the oyster genome, located in 3,595 scaffolds with a length of ~509.4 million; the average interval spacing was 4,210 bp. In addition, 111,158 SNPs were distributed in 21,050 coding genes, with an average of 5.3 SNPs per gene. In comparison with genotypes obtained through re-sequencing, ~69% of the converted SNPs had a concordance rate of >0.971; the mean concordance rate was 0.966. Evaluation based on genotypes of full-sib family individuals revealed that the average genotyping accuracy rate was 0.975. Carrying 133 K polymorphic SNPs, our oyster 190K SNP array is the first commercially available high-density SNP chip for mollusks, with the highest throughput. It represents a valuable tool for oyster genome-wide association studies, fine linkage mapping, and population genetics.