Hepatitis B virus X protein promotes MAN1B1 expression by enhancing stability of GRP78 via TRIM25 to facilitate hepatocarcinogenesis.

BACKGROUND: GRP78 has been implicated in hepatocarcinogenesis. However, the clinical relevance, biological functions and related regulatory mechanisms of GRP78 in hepatitis B virus (HBV)-associated hepatoma carcinoma (HCC) remain elusive. METHODS: The association between GRP78 expression and HBV-related HCC was investigated. The effects of HBV X protein (HBX) on GRP78 and MAN1B1 expression, biological functions of GRP78 and MAN1B1 in HBX-mediated HCC cells and mechanisms related to TRIM25 on GRP78 upregulation to induce MAN1B1 expression in HBX-related HCC cells were examined. RESULTS: GRP78 expression was correlated with poor prognosis in HBV-positive HCC. HBX increased MAN1B1 protein expression depending on GRP78, and HBX enhanced the levels of MAN1B1 to promote proliferation, migration and PI3-K/mTOR signalling pathway activation in HCC cells. GRP78 activates Smad4 via its interaction with Smad4 to increase MAN1B1 expression in HBX-expressing HCC cells. TRIM25 enhanced the stability of GRP78 by inhibiting its ubiquitination. HBX binds to GRP78 and TRIM25 and accelerates their interaction of GRP78 and TRIM25, leading to an increase in GRP78 expression. CONCLUSIONS: HBX enhances the stability of GRP78 through TRIM25 to increase the expression of MAN1B1 to facilitate tumorigenesis, and we provide new insights into the molecular mechanisms underlying HBV-induced malignancy.

Chryseobacterium pyrolae sp. nov., isolated from the rhizosphere soil of Pyrola calliantha H.

A novel Gram-stain-negative, aerobic, non-motile, rod-shaped bacterium, designated pc2-12T, was isolated from the rhizosphere soil of the herb Pyrola calliantha collected from arid areas of Tibet. The strain grew most vigorously with 1 % (w/v) NaCl, at pH 7.0 and at 25 °C. According to the results of 16S rRNA gene sequence analysis, pc2-12T was closely related to the members of the genus Chryseobacterium, with highest levels of sequence similarity to Chryseobacterium viscerum 687B-08T (98.42 %), Chryseobacterium oncorhynchi 701B-08T (98.11 %) and Chryseobacterium ureilyticum DSM 18017T (97.98 %). The average nucleotide identity values between pc2-12T and C. viscerum 687B-08T, C. oncorhynchi 701B-08T and C. ureilyticum DSM 18017T were 79.71, 79.49 and 79.26 %, respectively. The in silico DNA-DNA hybridisation values between pc2-12T and C. viscerum 687B-08T, C. oncorhynchi 701B-08T and C. ureilyticum DSM 18017T were 23.30, 23.00 and 22.90 %, respectively. The draft genome sequence of pc2-12T was 4.64 Mb long, with DNA G+C content of 37.0 mol%. The fatty acids contained in the cells of pc2-12T were mainly composed of iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c). The main polar lipid was phosphatidylethanolamine. MK-6 was the sole respiratory quinone. On the basis of the results of analysis of all the data described, pc2-12T is considered to represent a novel species of the genus Chryseobacterium, for which the name Chryseobacterium pyrolae sp. nov., is proposed. The type strain is pc2-12T (=GDMCC 1.3256T= JCM 35712T).

Pseudomonas tumuqii sp. nov., isolated from greenhouse soil.

A Gram-stain-negative, aerobic, rod-shaped and motile bacterium, named LAMW06T, was isolated from greenhouse soil in Beijing, China. In the 16S rRNA gene sequence comparison, strain LAMW06T had the highest similarity with Pseudomonas cuatrocienegasensis 1NT. Phylogenetic analysis based on the 16S rRNA and three housekeeping gene sequences (gyrB, rpoB and rpoD) indicated that strain represented a member of the genus Pseudomonas. The genome sequence size of the isolate was 5.5 Mb, with a DNA G + C content of 63.5 mol%. The average nucleotide identity and DNA-DNA hybridization values between strain LAMW06T and closely related members of Pseudomonas borbori R-20821T, Pseudomonas taeanensis MS-3T and P. cuatrocienegasensis 1NT were 90.9%, 82.4%, 81.5% and 43.0%, 25.9%, 24.6% respectively. The major fatty acids contained summed feature 3 (C16:1 ω6c and/or C16:1 ω7c), C18:1 ω7c and C16:0. The primary respiratory quinone was ubiquinone-9. The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, six aminophospholipids, six phospholipids, one aminolipid and one glycolipid. According to the genotypic, phylogenetic and chemotaxonomic data, strain LAMW06T represents a novel species within the genus Pseudomonas, for which the name Pseudomonas tumuqii sp. nov. is proposed. The type strain is LAMW06T (= GDMCC 1.2003T = KCTC 72829T).

Microbacterium sulfonylureivorans sp. nov., isolated from sulfonylurea herbicides degrading consortium.

A novel Gram-stain positive, aerobic, motile, rod-shaped bacterium, designated strain LAM7116T was isolated from a sulfonylurea herbicides degrading consortium enriched with birch forest soil from Xinjiang. Phylogenetic analysis based on the 16S rRNA gene sequences indicated that strain LAM7116T was closely related to the members of the genus Microbacterium, with the highest similarity to Microbacterium flavescens DSM 20643T (98.48%) and Microbacterium kitamiense Kitami C2T (98.48%). Strain LAM7116T formed a distinct subclade with M. flavescens DSM 20643T within the genus Microbacterium in the 16S rRNA gene phylogenetic trees. The genomic DNA G + C content of LAM7116T was 69.9 mol%. The digital DNA-DNA hybridization (dDDH) value between strain LAM7116T and M. flavescens DSM 20643T was 27.20%. The average nucleotide identity (ANI) value was 83.96% by comparing the draft genome sequences of strain LAM7116T and M. flavescens DSM 20643T. The major fatty acids were anteiso-C15:0, anteiso-C17:0, iso-C17:0, and iso-C16:0. The respiratory menaquinones of strain LAM7116T were MK-13 and MK-14. The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol, an unidentified lipid, and an unidentified glycolipid. The peptidoglycan contained the amino acids glycine, lysine, alanine, and glutamic acid. Based on the phenotypic characteristics and genotypic analyses, we consider that strain LAM7116T represents a novel species, for which the name Microbacterium sulfonylureivorans sp. nov. was proposed. The type strain is LAM7116T (= CGMCC 1.16620T = JCM 32823T). Strain LAM7116T secreted auxin IAA and grew well in Ashby nitrogen-free culture medium. Genomic results showed that strain LAM7116T carried the nitrogenase iron protein (nifU and nifR3) gene, which indicated that strain LAM7116T has the potential to fix nitrogen and promote plant growth. At same time, strain LAM7116T can degrade nicosulfuron (a kind of sulfonylurea herbicides) using glucose as carbon source. Microbacterium sulfonylureivorans sp. nov. LAM7116T is a potential candidate for the biofertilizers of organic agriculture areas, and may possess potential to be used in bioremediation of nicosulfuron-contaminated environments.

Chryseobacterium subflavum sp. nov., isolated from soil.

A Gram-stain-negative, aerobic, non-motile, rod-shaped bacterium, designated LAMRS1T, was isolated from a soil sample collected in Hebei Province, PR China. Strain LAMRS1T was able to grow optimally in the presence of 0.5 % (w/v) NaCl, at pH 7.5 and at 30 °C. On the basis of 16S rRNA gene sequence analysis, strain LAMRS1T was closely related to members of the genus Chryseobacterium, with highest levels of sequence similarity to Chryseobacterium soli DSM 19298T (97.9 %), Chryseobacterium soldanellicola DSM 17072T (97.6%) and Chryseobacterium piperi CTMT (97.5 %). The average nucleotide identity and digital DNA-DNA hybridization values between LAMRS1T and the closely related species of C. soli DSM 19298T, C. soldanellicola DSM 17072T and C. piperi CTMT were 78.1, 78.2 and 80.7 %, and 21.7, 22.0 and 23.7 %, respectively. The draft genome sequence of LAMRS1T was 4.61 Mb, with DNA G+C content of 36.2 mol%. The major isoprenoid quinone was menaquinone-6 and iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c) constituted the major cellular fatty acids. The main polar lipids were phosphatidylethanolamine, four aminolipids, three glycolipids and seven unidentified lipids. On the basis of evidence presented in this study, strain LAMRS1T represents a novel species of the genus Chryseobacterium, for which the name Chryseobacterium subflavum sp. nov. is proposed. The type strain is LAMRS1T (=JCM 33868T=KCTC 72823T).

Sporosarcina jiandibaonis sp. nov., isolated from saline soil.

A Gram-stain-positive, aerobic, motile, rod-shaped bacterium, designated strain LAM9210T, was isolated from a saline soil sample collected from Lingxian County, Shandong Province, PR China. Analysis of the 16S rRNA gene sequence of the isolate revealed highest sequence similarities to the type strain of Sporosarcina pasteurii NCIMB 8841T (97.6 % sequence similarity). The genomic G+C content was 40.4 mol%. The average nucleotide identity and in silico DNA-DNA hybridization values between strain LAM9210T and the type strain of the most closely related species S. pasteurii NCIMB 8841T were 73.6 and 20.6 %, respectively. Strain LAM9210T was found to grow at 10-40 °C (optimum, 30 °C), at pH 6.0-10.0 (optimum, pH 9.0) and with 0-6 % (w/v) NaCl (optimum, 0.5 %), respectively. The major fatty acids were anteiso-C15 : 0 and iso-C14 : 0. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and one unidentified phospholipid. Menaquinone-7 was detected as the predorminant respiratory quinone. Strain LAM9210T contained glycine, lysine, alanine and glutamic acid as the diagnostic amino acids in the cell-wall peptidoglycan. On the basis of phenotypic, phylogenetic and genotypic data, strain LAM9210T is considered to represent a novel species of the genus Sporosarcina, for which the name Sporosarcina jiandibaonis sp. nov. is proposed. The type strain is LAM9210T (=CGMCC 1.18607T=GDMCC 1.2002T=JCM 32514T).

Leucobacter chinensis sp. nov., with plant growth-promoting potential isolated from field soil after seven-years continuous maize cropping.

A novel Gram-stain-positive, aerobic, non-motile and rod-shaped bacterium, designated strain NC76-1T, was isolated from soil from a field that had undergone seven years continuous maize cropping from Liuba town located in Zhangye city, Gansu province, PR China. Colonies of strain NC76-1T were white, opaque and circular with a convex shape. The isolate was found to be able to grow at 10-40 °C (optimum 30 °C), pH 6.0 to 12.0 (optimum 7.0-8.0) and with 0-5.0 % (w/v) NaCl (optimum 0%). On the basis of the results of 16S rRNA gene sequence analysis, the strain fell within the clade of the genus Leucobacter, showing the highest sequence similarities with Leucobacter iarius 40T (97.4%), Leucobacter aridicollis CIP 108388T (97.0%), Leucobacter chromiireducens subsp. solipictus TAN 31504T (96.7%) and Leucobacter denitrificans M1T8B10T (96.7%). The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between NC76-1T and its closest relatives, L. iarius 40T, L. aridicollis CIP 108388T, L. chromiireducens subsp. solipictus TAN 31504T and L. denitrificans M1T8B10T were ≤73.5 % and 20.3%, respectively. The genomic DNA G+C content of NC76-1T was 61.5 mol%. It presented MK-11 as the predominant menaquinone. The major cellular fatty acids were anteiso-C15 : 0 (49.2 %) and iso-C16 : 0 (35.7%). The major polar lipids were found to be diphosphatidyglycerol, phosphatidylglycerol, phosphatidylethanolamine, aminoglycolipid, five glycolipid and one unidentified lipids. The cell wall amino acids were 2,4-diaminobutyric acid, alanine, glutamic acid, glycine and threonine. On the basis of the phylogenetic, phenotypic and chemotaxonomic characteristics, strain NC76-1T is concluded to represent a novel species within the genus Leucobacter, for which the name Leucobacter chinensis sp. nov. is proposed. The type strain is NC76-1T (GDMCC 1.2286T= JCM 34651T).

The interaction of canonical Wnt/ß-catenin signaling with protein lysine acetylation.

Canonical Wnt/ß-catenin signaling is a complex cell-communication mechanism that has a central role in the progression of various cancers. The cellular factors that participate in the regulation of this signaling are still not fully elucidated. Lysine acetylation is a significant protein modification which facilitates reversible regulation of the target protein function dependent on the activity of lysine acetyltransferases (KATs) and the catalytic function of lysine deacetylases (KDACs). Protein lysine acetylation has been classified into histone acetylation and non-histone protein acetylation. Histone acetylation is a kind of epigenetic modification, and it can modulate the transcription of important biological molecules in Wnt/ß-catenin signaling. Additionally, as a type of post-translational modification, non-histone acetylation directly alters the function of the core molecules in Wnt/ß-catenin signaling. Conversely, this signaling can regulate the expression and function of target molecules based on histone or non-histone protein acetylation. To date, various inhibitors targeting KATs and KDACs have been discovered, and some of these inhibitors exert their anti-tumor activity via blocking Wnt/ß-catenin signaling. Here, we discuss the available evidence in understanding the complicated interaction of protein lysine acetylation with Wnt/ß-catenin signaling, and lysine acetylation as a new target for cancer therapy via controlling this signaling.

Cellular retinol binding protein-1 inhibits cancer stemness via upregulating WIF1 to suppress Wnt/ß-catenin pathway in hepatocellular carcinoma.

BACKGROUND: CRBP-1, a cytosolic chaperone of vitamin A, is identified in a serious number of cancers; however, its biological role in hepatocellular carcinoma (HCC) needs to be further explored. The aim of our present study is to explore the roles and mechanisms of CRBP-1 in regulating liver cancer by using in vitro and in vivo biology approaches. METHODS: The expression level of CRBP-1 was detected using immunohistochemistry in HCC and matching adjacent non-tumorous liver tissues. Following established stable CRBP-1 overexpressed HCC cell lines, the cell growth and tumorigenicity were investigated both in vitro and in vivo. Intracellular retinoic acid was quantified by ELISA. The relationship between CRBP-1 and WIF1 was validated by using dual luciferase and ChIP analyses. RESULTS: The low expression of CRBP-1 was observed in HCC tissues compared to the normal liver tissues, while high CRBP-1 expression correlated with clinicopathological characteristics and increased overall survival in HCC patients. Overexpression of CRBP-1 significantly inhibited cell growth and tumorigenicity both in vitro and in vivo. Moreover, overexpression of CRBP-1 suppressed tumorsphere formation and cancer stemness related genes expression in HCC. Mechanically, CRBP-1 inhibited Wnt/ß-catenin signaling pathway to suppress cancer cell stemness of HCC. Furthermore, our results revealed that CRBP-1 could increase the intracellular levels of retinoic acid, which induced the activation of RARs/RXRs leading to the transcriptional expression of WIF1, a secreted antagonist of the Wnt/ß-catenin signaling pathway, by physically interacting with the region on WIF1 promoter. CONCLUSION: Our findings reveal that CRBP-1 is a crucial player in the initiation and progression of HCC, which provide a novel independent prognostic biomarker and therapeutic target for the diagnosis and treatment of HCC.

Calcium signaling in hepatitis B virus infection and its potential as a therapeutic target.

As a ubiquitous second messenger, calcium (Ca2+) can interact with numerous cellular proteins to regulate multiple physiological processes and participate in a variety of diseases, including hepatitis B virus (HBV) infection, which is a major cause of hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. In recent years, several studies have demonstrated that depends on the distinct Ca2+ channels on the plasma membrane, endoplasmic reticulum, as well as mitochondria, HBV can elevate cytosolic Ca2+ levels. Moreover, within HBV-infected cells, the activation of intracellular Ca2+ signaling contributes to viral replication via multiple molecular mechanisms. Besides, the available evidence indicates that targeting Ca2+ signaling by suitable pharmaceuticals is a potent approach for the treatment of HBV infection. In the present review, we summarized the molecular mechanisms related to the elevation of Ca2+ signaling induced by HBV to modulate viral propagation and the recent advances in Ca2+ signaling as a potential therapeutic target for HBV infection. Video Abstract.

Hepatitis B virus X protein promotes vimentin expression via LIM and SH3 domain protein 1 to facilitate epithelial-mesenchymal transition and hepatocarcinogenesis.

BACKGROUND: Hepatitis B virus (HBV) X protein (HBX) has been reported to be responsible for the epithelial-mesenchymal transition (EMT) in HBV-related hepatocellular carcinoma (HCC). Vimentin is an EMT-related molecular marker. However, the importance of vimentin in the pathogenesis of HCC mediated by HBX has not been well determined. METHODS: The expression of vimentin induced by HBX, and the role of LIM and SH3 domain protein 1 (LASP1) in HBX-induced vimentin expression in hepatoma cells were examined by western blot and immunohistochemistry analysis. Both the signal pathways involved in the expression of vimentin, the interaction of HBX with vimentin and LASP1, and the stability of vimentin mediated by LASP1 in HBX-positive cells were assessed by western blot, Co-immunoprecipitation, and GST-pull down assay. The role of vimentin in EMT, proliferation, and migration of HCC cells mediated by HBX and LASP1 were explored with western blot, CCK-8 assay, plate clone formation assay, transwell assay, and wound healing assay. RESULTS: Vimentin expression was increased in both HBX-positive hepatoma cells and HBV-related HCC tissues, and the expression of vimentin was correlated with HBX in HBV-related HCC tissues. Functionally, vimentin was contributed to the EMT, proliferation, and migration of hepatoma cells mediated by HBX. The mechanistic analysis suggested that HBX was able to enhance the expression of vimentin through LASP1. On the one hand, PI3-K, ERK, and STAT3 signal pathways were involved in the upregulation of vimentin mediated by LASP1 in HBX-positive hepatoma cells. On the other hand, HBX could directly interact with vimentin and LASP1, and dependent on LASP1, HBX was capable of promoting the stability of vimentin via protecting it from ubiquitination mediated protein degradation. Besides these, vimentin was involved in the growth and migration of hepatoma cells mediated by LASP1 in HBX-positive hepatoma cells. CONCLUSION: Taken together, these findings demonstrate that, dependent on LASP1, vimentin is crucial for HBX-mediated EMT and hepatocarcinogenesis, and may serve as a potential target for HBV-related HCC treatment. Video abstract.

Arthrobacter sulfonylureivorans sp. nov., isolated from a sulfonylurea herbicides degrading consortium enriched with birch forest soil.

A gram-stain positive, aerobic, motile, rod-shaped bacterium, designated strain LAM7117T, was isolated from a sulfonylurea herbicides degrading consortium enriched with birch forest soil. The optimal temperature and pH for the growth of strain LAM7117T were 35 °C and 7.5, respectively. Strain LAM7117T could grow in the presence of NaCl with concentration up to 9% (w/v). Strain LAM7117T formed a distinct phylogenetic subclade within the genus Arthrobacter in the phylogenetic trees built with 16S rRNA gene sequences and shared the highest similarity with A. crystallopoietes JCM 2522T (97.7%). The values of digital DNA-DNA relatedness and Avery Nucleotide Identity based on the genome sequences between LAM7117T and A. crystallopoietes JCM 2522T were 21.4 and 77.4%, respectively. The genomic DNA G + C content was 65.9 mol%. The major cellular fatty acids were anteiso-C15:0, iso-C16:0 and anteiso-C17:0. The cell wall peptidoglycan contained the amino acids as glycine, lysine, alanine and glutamic acid. The major polar lipids present in strain LAM7117T were diphosphatidylglycerol, phosphatidylglycerol, phosphatidyl inositol, two unidentified glycolipids and one unidentified lipid. The predominant menaquinones of strain LAM7117T were MK-8 and MK-9. Based on the phenotypic characteristics, chemotaxonomic data and genotypic analyses, strain LAM7117T should be classified as a novel species of genus Arthrobacter, for which the name Arthrobacter sulfonylureivorans sp. nov. is proposed. The type strain is LAM7117T (= JCM 32824T = CGMCC 1.16681T).

Pseudomonas nicosulfuronedens sp. nov., a nicosulfuron degrading bacterium, isolated from a microbial consortium.

A Gram-stain-negative, aerobic, motile, short-rod-shaped bacterium with nicosulfuron-degrading ability, designated strain LAM1902T, was isolated from a microbial consortium enriched with nicosulfuron as a sole nitrogen and energy source. The optimal temperature and pH for growth of strain LAM1902T were 30 °C and pH 6.0, respectively. Strain LAM1902T could grow in the presence of NaCl with concentration up to 4.0 % (w/v). Comparative analysis of 16S rRNA gene sequences revealed that LAM1902T was closely related to the members of the family Pseudomonadaceae to the genus Pseudomonas, with the highest similarity to Pseudomonas nitroreducens DSM 14399T (99.6 %), Pseudomonas nitritireducens WZBFD3-5A2T (99.3 %) and Pseudomonas panipatensis Esp-1T (98.8 %). Multi-locus sequence analysis based on both concatenated sequences of the 16S rRNA gene and three housekeeping genes (gyrB, rpoB and rpoD) further confirmed the intrageneric phylogenetic position of strain LAM1902T. The genomic DNA G+C content of LAM1902T was 64.8 mol%. The low values of in silico DNA-DNA hybridization (less than 43.7 %) and average nucleotide identity (less than 90.9 %) also showed that the strain was distinctly different from known species of the genus Pseudomonas. The major fatty acids were C16 : 0, C17 : 0 cyclo and anteiso C15 : 0. Ubiquinone Q-9 was detected as the predorminant respiratory quinone. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and aminophospholipid. Based on phylogenetic, phenotypic and chemotaxonomic analyses and genome comparisons, we conclude that strain LAM1902T represents a novel species, for which the name Pseudomonas nicosulfuronedens sp. nov. is proposed. The type strain is LAM1902T (=JCM 33860T=KCTC 72830T).

Hepatitis B virus core protein promotes the expression of neuraminidase 1 to facilitate hepatocarcinogenesis.

Neuraminidase 1 (NEU1) has been reported to be associated with hepatocellular carcinoma (HCC). However, the function and associated molecular mechanisms of NEU1 in hepatitis B virus (HBV)-related HCC have not been well investigated. In the present study, the expression of NEU1 mediated by HBV and HBV core protein (HBc) was measured in hepatoma cells. The expression of NEU1 protein was detected via immunohistochemical analysis in HBV-associated HCC tissues. The role of NEU1 in the activation of signaling pathways and epithelial-mesenchymal transition (EMT) and the proliferation and migration of hepatoma cells mediated by HBc was assessed. We found that NEU1 was upregulated in HBV-positive hepatoma cells and HBV-related HCC tissues. HBV promoted NEU1 expression at the mRNA and protein level via HBc in hepatoma cells. Mechanistically, HBc was able to enhance the activity of the NEU1 promoter through NF-κB binding sites. In addition, through the increase in NEU1 expression, HBc contributed to activation of downstream signaling pathways and EMT in hepatoma cells. Moreover, NEU1 facilitated the proliferation and migration of hepatoma cells mediated by HBc. Taken together, our findings provide novel insight into the molecular mechanism underlying the oncogenesis mediated by HBc and demonstrate that NEU1 plays a vital role in HBc-mediated functional abnormality in HCC. Thus, NEU1 may serve as a potential therapeutic target in HBV-associated HCC.

Prognostic implications of alcohol dehydrogenases in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignancy with high incidence and mortality rates worldwide. Alcohol dehydrogenases (ADHs) are huge family of dehydrogenase enzymes and associated with the prognosis of various cancers. However, comprehensive analysis of prognostic implications related to ADHs in HCC is still lacking and largely unknown. METHODS: The expression profiles and corresponding clinical information of HCC were obtained from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test was employed to evaluate the expression of ADHs. Cox regression and Kaplan-Meier analyses were used to investigate the association between clinicopathological characteristics and survival. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses were performed and visualized using R/BiocManager package. RESULTS: We found that the expression of ADH1A, ADH1B, ADH1C, ADH4, and ADH6 was significantly downregulated in HCC samples compared to normal liver samples. Our univariate and multivariate Cox regression analyses results showed that high expression of ADH1A, ADH1B, ADH1C, ADH4, and ADH6 was considered as an independent factor with an improved prognosis for the survival of HCC patients. Moreover, our Kaplan-Meier analysis results also revealed that high expression of AHD1A, ADH1B, ADH1C, ADH4, and ADH6 was significantly associated with good survival rate in HCC patients. In addition, GO, KEGG, and GSEA analyses unveiled several oncogenic signaling pathways were negatively associated high expression of ADHs in HCC. CONCLUSION: In the present study, our results provide the potential prognostic biomarkers or molecular targets for the patients with HCC.

Streptomyces soli sp. nov., isolated from birch forest soil.

A Gram-staining positive, aerobic, non-motile, rod-shaped bacterium, designated strain LAM7114T, was isolated from soil sample collected from a birch forest in Xinjiang Uygur Autonomous Region, China. The optimal temperature and pH for the growth of strain LAM7114T were 30 °C and 7.0, respectively. Strain LAM7114T could grow in the presence of NaCl up to 10% (w/v). Comparative analysis of the 16S rRNA gene sequences revealed that LAM7114T was closely related to the members of the family genus Streptomyces, with the highest similarity to Streptomyces urticae NEAU-PCY-1T (98.3%) and Streptomyces fildesensis GW25-5T (98.2%). The genomic G + C content was 70.0 mol%. The DNA-DNA hybridization values between strain LAM7114T and S. urticae CCTCC AA 2017015T, S. fildesensis CGMCC 4.5735T were 32.5 ± 1.8% and 27.5 ± 2.6%, respectively. The cell wall contained LL-diaminopimelic acid as the diagnostic diamino acid in the peptidoglycan. The whole-cell hydrolysates included glucose and mannose. The major fatty acids were anteiso-C15:0, iso-C15:0 and iso-C16:0. The predominant menaquinones were MK-9(H6), MK-9(H4) and MK-9(H8). The main polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, three unidentified aminophospholipids, three unidentified phospholipids, and an unidentified aminolipid. Based on the phenotypic characteristics and genotypic analyses, we propose that strain LAM7114T represents a novel species in the genus Streptomyces, for which the name Streptomyces soli sp. nov. is proposed. The type strain is LAM7114T (= CGMCC 4.7581T = JCM 32822T).

Paenibacillus solisilvae sp. nov., isolated from birch forest soil.

A Gram-stain-positive, motile, rod-shaped bacterium, designated strain LAM7113T, was isolated from soil sample collected from a birch forest in Xinjiang Uygur Autonomous Region, PR China. Strain LAM7113T grew optimally at pH 8.0, 30 °C and in the presence of 1.0 % NaCl (w/v). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain LAM7113T was closely related to members of the genus Paenibacillus, with the highest similarity to Paenibacillus baekrokdamisoli Back-11T (96.2 %). The genomic DNA G+C content was 43.4 mol%. The values of average nucleotide identity and DNA-DNA hybridization were 66.1 and 27.0 %, respectively, by comparing the draft genome sequences of strain LAM7113T and P. baekrokdamisoli Back-11T. Anteiso-C15 : 0 and iso-C15 : 0 were identified as the major cellular fatty acids. Menaquinone-7 was detected as the predominant respiratory quinone. The major polar lipids were found to be diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, three unidentified aminophospholipids, three unidentified glycolipids, one unidentified phospholipid and two unknown polar lipids. Based on its phenotypic, phylogenetic and chemotaxonomic characteristics, strain LAM7113T is proposed to represent a novel species of the genus Paenibacillus with the name Paenibacillus solisilvae sp. nov. The type strain is LAM7113T (=CGMCC 1.16619T=JCM 32513T).

Actinoplanes solisilvae sp. nov., Isolated from Birch Forest Soil.

A novel actinomycete, designated strain LAM7112T, was isolated from soil sample collected from a birch forest in Xinjiang Uygur Autonomous Region, China. The new isolate was found to be able to grow at 20-45 °C (optimum: 35 °C), pH 5.0-10.0 (optimum: 7.0) and in the presence of 0-10.0% (optimum: 3.0%) (w/v) NaCl. The isolate formed very scantily irregular sporangia containing motile spores on the substrate mycelium. Phylogenetic analysis of 16S rRNA gene sequences indicated that the new isolate was closely related to members of the family Micromonosporaceae, with highest similarites to Actinoplanes ferrugineus X-14695T (97.4%), Micromonospora zamorensis DSM 45600T (97.3%) and Micromonospora aurantiaca ATCC 27029T (97.3%). In the phylogenetic trees, strain LAM7112T formed a stable phylogenetic subclade within the genus Actinoplanes. The genomic DNA G + C content was 70.0 mol%. The major fatty acids (> 10%) were determined to be iso-C16:0, anteiso-C15:0 and anteiso-C17:0. The predominant menaquinones were identified as MK-9 (H2), MK-9 (H4) and MK-9 (H6). The major polar lipids were found to be diphosphatidylglycerol, phosphatidylinositol and phosphatidylethanolamine. The diagnostic amino acid of the cell wall peptidoglycan was determined to be meso-diaminopimelic acid. The diagnostic sugars in cell hydrolysates were determined to be glucose and ribose. On the basis of its phenotypic, phylogenetic and chemotaxonomic characteristics, strain LAM7112T (= CGMCC 4.7580T = JCM 32512T) is proposed to represent the type strain of a novel species of the genus Actinoplanes, for which the name Actinoplanes solisilvae is proposed.

The interaction of hepatitis B virus with the ubiquitin proteasome system in viral replication and associated pathogenesis.

BACKGROUND: The ubiquitin proteasome system (UPS) regulates the expression levels of cellular proteins by ubiquitination of protein substrates followed by their degradation via the proteasome. As a highly conserved cellular degradation mechanism, the UPS affects a variety of biological processes and participates in viral propagation. MAIN BODY: During hepatitis B virus (HBV) infection, the UPS is shown to act as a double-edged sword in viral pathogenesis. On the one hand, the UPS acts as a host defense mechanism to selectively recognize HBV proteins as well as special cellular proteins that favor the viral life cycle and induces their ubiquitin-dependent proteasomal degradation to limit HBV infection. On the other hand, the HBV has evolved to subvert the UPS function for its own advantage. Moreover, in the infected hepatocytes, certain cellular proteins that are dependent on the UPS are involved in abnormal biological processes which are mediated by HBV. CONCLUSION: The molecular interaction of HBV with the UPS to modulate viral propagation and pathogenesis is summarized in the review. Considering the important role of the UPS in HBV infection, a better understanding of the HBV-UPS interaction could provide novel insight into the mechanisms that are involved in viral replication and pathogenesis and help to develop potential treatment strategies targeting the UPS.

Photobacterium salinisoli sp. nov., isolated from a sulfonylurea herbicide-degrading consortium enriched with saline soil.

A Gram-stain-negative, aerobic, motile, rod-shaped bacterium, designated strain LAM9072T, was isolated from a sample of a sulfonylurea herbicide-degrading consortium enriched with saline soil. The optimal temperature and pH for the growth of strain LAM9072T were 35 °C and 7.0, respectively. Strain LAM9072T could grow in the presence of NaCl up to 9 % (w/v). Comparative analysis of the 16S rRNA gene sequences revealed that strain LAM9072T was closely related to members of the family Vibrionaceae, with the highest similarities to Photobacterium halotolerans MACL01T (97.7 %) and Photobacterium galatheae S2753T (97.7 %). Strain LAM9072T formed a distinct phylogenetic subclade within the genus Photobacterium in the 16S rRNA gene phylogenetic trees. The results of multi-locus sequence analysis revealed a distinct lineage with P. halotolerans MACL01T as its closest relative. The genomic G+C content was 50.2 mol%. The DNA-DNA hybridization values between strain LAM9072T and P. halotolerans LMG 22194T and P. galatheae LMG 28894T were 41.6 and 22.2 %, respectively. The average nucleotide identity values were 90.9 and 78.8 %, respectively, by comparing the draft genome sequences of strain LAM9072T and P. halotolerans LMG 22194T and P. galatheae LMG 28894T. The major fatty acids were summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c), C16 : 0 and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). Ubiquinone 8 was detected as the predominant respiratory quinone. The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, aminophospholipid and four unidentified lipids. Based on its phenotypic characteristics and the results of genotypic analyses, we propose that strain LAM9072T represents a novel species, for which the name Photobacteriumsalinisoli sp. nov. is proposed. The type strain is LAM9072T (=ACCC 19961T=JCM 30852T).