Research on the Low-Temperature Impact Toughness of a New 100-mm Ultra-Thick Offshore Steel Fabricated Using the Narrow-Gap Laser Wire Filling Welding Process.

Ultra-thick offshore steel, known for its high strength, high toughness, and corrosion resistance, is commonly used in marine platforms and ship components. However, when offshore steel is in service for an extended period under conditions of high pressure, extreme cold, and high-frequency impact loads, the weld joints are prone to fatigue failure or even fractures. Addressing these issues, this study designed a narrow-gap laser wire filling welding process and successfully welded a 100-mm new type of ultra-thick offshore steel. Using finite element simulation, EBSD testing, SEM analysis, and impact experiments, this study investigates the weld's microstructure, impact toughness, and fracture mechanisms. The research found that at -80 °C, the welded joint exhibited good impact toughness (>80 J), with the impact absorption energy on the surface of the weld being 217.7 J, similar to that of the base material (225.3 J), and the fracture mechanism was primarily a ductile fracture. The impact absorption energy in the core of the weld was 103.7 J, with the fracture mechanism mainly being a brittle fracture. The EBSD results indicated that due to the influence of the welding thermal cycle and the cooling effect of the narrow-gap process, the grains gradually coarsened from the surface of the welded plate to the core of the weld, which was the main reason for the decreased impact toughness at the joint core. This study demonstrates the feasibility of using narrow-gap laser wire filling welding for 100-mm new type ultra-thick offshore steel and provides a new approach for the joining of ultra-thick steel plates.

HGF/c-Met signaling promotes the migration and proliferation of deer antler MSCs.

The complete regeneration of deer antlers is based on the proliferation and differentiation of stem cells. Mesenchymal stem cells (MSCs) of antlers have an important role in antler regeneration and rapid growth and development. HGF is mainly synthesized and secreted by mesenchymal cells. After binding to its receptor c-Met, which transduces signals into cells to stimulate cell proliferation and migration in various organs to promote tissue morphogenesis and angiogenesis. However, the role and mechanism of the HGF/c-Met signaling pathway on antler MSCs are still unclear. In this study, we established antler MSCs with overexpression and interference of HGF gene by lentivirus and small interference RNA, observed the effect of HGF/c-Met signal pathway on the proliferation and migration of antler MSCs, and detected the expression of downstream related signal pathway genes, to explore the mechanism of HGF/c-MET signal pathway on the proliferation and migration of antler MSCs. The results showed that the HGF/c-Met signal affects the expression of RAS, ERK and MEK genes, regulates the proliferation of pilose antler MSCs through Ras/Raf, MEK/ERK pathway, affects the expression of Gab1, Grb2, AKT and PI3K genes, and regulates the migration of MSCs of pilose antler through Gab1/Grb2 and PI3K/AKT pathway.

Study on the mechanism of Fufang E'jiao Jiang on precancerous lesions of gastric cancer based on network pharmacology and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang E'jiao Jiang (FEJ) is a prominent traditional Chinese medicine prescription, which consists of Asini Corii Colla (Donkey-hide gelatin prepared by stewing and concentrating from the hide of Equus asinus Linnaeus., ACC), Codonopsis Radix (the dried roots of Codonopsis pilosula (Franch.) Nannf., CR), Ginseng Radix et Rhizoma Rubra (the steamed and dried root of Panax ginseng C.A. Mey., GRR), Crataegi Fructus (the mature fruits of Crataegus pinnatifida Bunge., CF), and Rehmanniae Radix Praeparata (the steamed and sun dried tuber of Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & C.A. Mey., RRP). It is a popularly used prescription for "nourishing Qi and nourishing blood". AIM OF THE STUDY: To explore the potential mechanism of FEJ on precancerous lesion of gastric cancer in rats by combining network pharmacology and metabolomics. METHODS: Traditional Chinese Medicine Systems Pharmacology and Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine were used to identify the ingredients and potential targets of FEJ. GeneCards database was used to define PLGC-associated targets. We built a herb-component-disease-target network and analyzed the protein-protein interaction network. Underlying mechanisms were identified using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. In addition, 40% ethanol, N-methyl-N'-nitro-N-nitroguanidine and irregular eating were used to establish PLGC rats model. We also evaluated the efficacy of FEJ on MNNG-induced PLGC rats by body weight, histopathology, blood routine and cytokine levels, while the predicted pathway was determined by the Western blot. Ultra-performance liquid chromatography-tandem mass spectrometry-based serum non-targeted metabolomics was used to select potential biomarkers and relevant pathways for FEJ in the treatment of PLGC. RESULTS: Network pharmacology showed that FEJ exhibited anti-PLGC effects through regulating ALB, TNF, VEGFA, TP53, AKT1 and other targets, and the potential pathways mainly involved cancer-related, TNF, PI3K-AKT, HIF-1, and other signaling pathways. Animal experiments illustrated that FEJ could suppress inflammation, regulate gastrointestinal hormones, and inhibit the expression of PI3K/AKT/HIF-1α pathway-related proteins. Based on serum non-targeted metabolomics analysis, 12 differential metabolites responding to FEJ treatment were identified, and metabolic pathway analysis showed that the role of FEJ was concentrated in 6 metabolic pathways. CONCLUSION: Based on network pharmacology, animal experiments and metabolomics, we found that FEJ might ameliorate gastric mucosal injury in PLGC rats by regulating gastrointestinal hormones and inhibiting inflammation, and its mechanism of action is related to the inhibition of excessive activation of PI3K/AKT/HIF-1α signaling pathway and regulation of disorders of body energy metabolism. This comprehensive strategy also provided a reasonable way for unveiling the pharmacodynamic mechanisms of multi-components, multi-targets, and multi-pathways in Traditional Chinese Medicine.

Supplementation of tea polyphenols in sludge Fenton oxidation improves sludge dewaterability and reduces chemicals consumption.

The Fenton oxidation improves sludge dewatering but faces notable technical and economic challenges, including a narrow acidic pH range, slow reduction of Fe(III), and the use of high doses of chemicals. Herein, we used a natural polyhydroxyphenol tea polyphenols (TP), as an iron redox conversion enhancer, to mitigate these issues. Compared with the classical Fenton process at pH 3.0, the process with TP (33.8 mg/g dry solids (DS)) improved sludge dewaterability at pH 7.5 in a Fenton-like system with faster Fe(II)/Fe(III) cycling and two times lower consumption of the Fenton reagent. Sludge capillary suction time and specific resistance to filtration decreased from 70 s to 22 s and from 2.7 × 1013 m/kg to 5.2 × 1011 m/kg, respectively, while the required doses of Fe(II) and H2O2 were cut to 25 mg/g DS and 31.2 mg/g DS. Mechanistically, TP could bond readily with Fe(II)/Fe(III) at neutral pH to form stable complexes with complexation constants of 34 ± 161 M-1 and 52 ± 70 M-1, respectively, and reduce part of the Fe(III) to Fe(II) simultaneously. This maintained sufficient soluble Fe in the sludge and boosted efficient conversion of Fe(II)/Fe(III) to yield more hydroxyl radicals (•OH). Subsequently, •OH oxidation resulted in the decomposition of biopolymers with a molecular weight of 108 Da (e.g., 58.2% of polysaccharides and 31.6% of proteins in tightly bound extracellular polymeric substances) into small molecules and disintegration of bioflocs into smaller particles with increased porosity, contact angle, and cell lysis; these changes helped reduce bound water content and improved sludge dewaterability. In addition, the TP-mediated Fenton process disinfected fecal coliforms in the sludge and preserved the sludge organic matters. This work proposes a new paradigm for developing cost-effective sludge dewatering technologies that relies on the synergistic effects of plant polyphenols and advanced oxidation processes.

Transcriptome changes of Takifugu obscurus liver after acute exposure to phenanthrene.

Phenanthrene (Phe) is a model compound in polycyclic aromatic hydrocarbon (PAH) research. Reportedly, Phe treatment induced oxidative stress and histological disorders to Takifugu obscurus liver. In this study, to further explore the molecular responses of T. obscurus liver to Phe exposure, transcriptome sequencing was applied to compare mRNA transcription profiles between Phe treatment and the control. Compared with the control, 1,581 and 1,428 genes were significantly upregulated and downregulated in Phe treatment, respectively. Further analysis revealed that Phe treatment mainly upregulated genes in Ras-MAPK and PI3K-akt signaling pathways, which represented insulin resistance and further activated the FOXO signaling pathway. The triacylglycerol biosynthesis was promoted but the gluconeogenesis process was inhibited in response to Phe treatment, demonstrating that Phe exposure disturbed the sugar and lipid metabolism. Moreover, Phe treatment upregulated the Apelin-APJ and ErbB signaling pathways, promoting angiogenesis in T. obscurus liver. Insulin resistance, promoted triacylglycerol biosynthesis, and angiogenesis might explain the molecular mechanisms underlying carcinogenic toxicity of Phe. Overall, this study provides new insights to understand the environmental risk of Phe to fishes.

Network pharmacology unveils spleen-fortifying effect of Codonopsis Radix on different gastric diseases based on theory of "same treatment for different diseases" in traditional Chinese medicine.

Objective: "Same treatment for different diseases" is a unique treatment strategy under the guidance of traditional Chinese medicine (TCM) theory. Codonopsis Radix (Codonopsis pilosula, Dangshen in Chinese) with spleen-fortifying effect was employed to understand the strategy of "Same treatment for different diseases", based on its common mechanism in the treatment of gastric diseases including gastric ulcer, gastritis and gastric cancer via network pharmacology research. Methods: Network pharmacology research methods were used to analyze the interaction network and potential mechanisms of Dangshen in treating gastric ulcer, gastritis and gastric cancer. The active components and their target proteins of Dangshen were integrated from TCMSP, BATMAN-TCM databases. The targets of gastric ulcer, gastritis and gastric cancer were collected through GeneCards, PubMed, TDD and DisGeNET Database. Through screening, the key components and the key targets of Dangshen in treating gastric ulcer, gastritis and gastric cancer were obtained. After KEGG pathway analysis and GO analysis, the important pathways and biological processes were analyzed. Results: Through data and literature mining, the common and specific pharmaceutical effects and mechanism of Dangshen were summarized in these three gastric lesions. It was shown that Dangshen mainly acted on gastric ulcer, gastritis and gastric cancer through the overall regulation of the PI3K-AKT signaling pathway. With the development of the disease, it will gradually increase the control of inflammation through TNF, NF-κB and other inflammation-related signaling pathways to reduce inflammatory damage. For tumorigenesis, it pays more attention to inhibiting the ErbB signaling pathways to reduce the proliferation and migration of tumor cells. In addition, Dangshen's regulation of HIF-1 signaling pathway may also be beneficial for the treatment of gastric ulcer, gastritis and gastric cancer. Conclusion: Dangshen achieves spleen-fortifying effect on gastric diseases including gastric ulcer, gastritis and gastric cancer through multiple targets in multiple pathways, especially PI3K-AKT pathway and HIF-1 pathway. It could provide a scientific basis for understanding the strategy of "Same treatment for different diseases" in traditional Chinese medicine.

Establishment of a novel virus-induced virulence effector assay for the identification of virulence effectors of plant pathogens using a PVX-based expression vector.

Plant pathogens deliver virulence effectors into plant cells to modulate plant immunity and facilitate infection. Although species-specific virulence effector screening approaches have been developed for several pathogens, these assays do not apply to pathogens that cannot be cultured and/or transformed outside of their hosts. Here, we established a rapid and parallel screening assay, called the virus-induced virulence effector (VIVE) assay, to identify putative effectors in various plant pathogens, including unculturable pathogens, using a virus-based expression vector. The VIVE assay uses the potato virus X (PVX) vector to transiently express candidate effector genes of various bacterial and fungal pathogens into Nicotiana benthamiana leaves. Using the VIVE assay, we successfully identified Avh148 as a potential virulence effector of Phytophthora sojae. Plants infected with PVX carrying Avh148 showed strong viral symptoms and high-level Avh148 and viral RNA accumulation. Analysis of P. sojae Avh148 deletion mutants and soybean hairy roots overexpressing Avh148 revealed that Avh148 is required for full pathogen virulence. In addition, the VIVE assay was optimized in N. benthamiana plants at different developmental stages across a range of Agrobacterium cell densities. Overall, we identified six novel virulence effectors from seven pathogens, thus demonstrating the broad effectiveness of the VIVE assay in plant pathology research.

Transcriptome changes of Takifugu obscurus liver after acute exposure to the oxygenated-PAH 9,10-phenanthrenequione.

Contamination with polycyclic aromatic hydrocarbons (PAHs) causes noticeable ecological problems in aquatic ecosystems. 9,10-Phenanthrenequione (9,10-PQ) is an oxidized PAH and is highly toxic to aquatic animals. However, the effects of 9,10-PQ on the molecular metabolism of fish remain largely unknown. In this study, Takifugu obscurus juveniles were acutely exposed to 44.30 µg/L 9,10-PQ for 3 days. The transcriptome profile changes in their livers were compared between the 9,10-PQ treatment group and the control using T. rubripes as the reference genome. The results identified 22,414 genes in our transcriptome. Among them, 767 genes were differentially expressed after exposure to 9,10-PQ, which enriched 16 KEGG pathways. Among them, the glycolysis, phagosome, and FOXO signaling pathways were significantly activated in 9,10-PQ treatment compared with the control. These data indicate that 9,10-PQ increased the glycolysis capacity to produce more energy for resistance and harmed immune function. Moreover, several genes related to tumorigenesis were significantly upregulated in response to 9,10-PQ, displaying the carcinogenic toxicity of 9,10-PQ to T. obscurus. Genes in steroid biosynthesis pathways were downregulated in the 9,10-PQ treatment group, suggesting interference with the endocrine system. Overall, these findings provide information to help evaluate the environmental risks that oxygenated-PAHs present to T. obscurus.

FoxL2 combined with Cyp19a1a regulate the spawning upstream migration in Coilia nasus.

FoxL2 is a member of the forkhead/HNF-3-related family of transcription factors which provides tissue specific gene regulation. It is known to regulate ovarian aromatase, which plays a crucial role in ovarian development and mature. To understand the role of FoxL2/ovarian aromatase encoded gene Cyp19a1a during ovarian development and recrudescence, we identified cDNA characteristics of FoxL2 and Cyp19a1a, analyzed its temporal expression both at transcript and protein levels in the anadromous fish, Coilia nasus. Tissue distribution pattern revealed that FoxL2 mRNA expression level was highest in ovary, while Cyp19a1a mRNA was highest in brain. During the upstream migration cycle, in ovary, the FoxL2 mRNA temporal expression peaked at the multiplication stage (stage III in May), the Cyp19a1a mRNA expression peaked at the onset stage (stage I in March). It was found that their mRNA transcripts were maintained at high level during the migration stage (from stage I in March to stage VI in July). Additionally, the strongest immunolabeling positive signals of Cyp19a1a and FoxL2 proteins were mainly found in the cytoplasm of olfactory bulb cell, stratum granulare and neurogliocyte cells and development stage oocytes. Data indicated that FoxL2 and Cyp19a1a were inducible and functional in the C. nasus ovary development and migration process. Therefore, the present results can be regarded as evidence for indispensable roles of FoxL2 and Cyp19a1a in the ovary development and migratory behavior at gene expression patterns and encoded protein distribution level.

A novel approach coupling ferrous iron bio-oxidation and ferric iron chemo-reduction to promote biomineralization in simulated acidic mine drainage.

A novel Acidithiobacillus ferrooxidans-mediated approach coupling biological oxidation and chemical reduction for treating acid mine drainage (AMD) was investigated. The results showed that controlled addition of zero valent iron (ZVI) into the coupling system did not exhibit a significant adverse influence on the bacterial activity of Acidithiobacillus ferrooxidans but markedly increased the formation of secondary Fe-minerals. Nutrition did not affect the efficiency of coupling process, except for the bacteria density of A. ferrooxidans. 2 days cyclic treatment performed better than that of 4 and 8 days. After 14 cycles of the coupling process, 89.4% of total iron (2.23 g L-1) was transferred into Fe-minerals finally. In addition, the combined system was highly effective in removing sulfate (63%) from a simulated AMD that contained soluble Cu, Zn, Al, and Mn. Valuable iron-sulfate material e.g. schwertmannite was formed with little co-precipitation of other metals. Therefore, the integration of A. ferrooxidans into the reduction by ZVI may have considerable potential in the enhancement of biomineralization efficiency, which may further decrease soluble TFe and sulfate loads in AMD before lime neutralization.

Identification of Biological Targets of Therapeutic Intervention for Hepatocellular Carcinoma by Integrated Bioinformatical Analysis.

BACKGROUND We screened the potential molecular targets and investigated the molecular mechanisms of hepatocellular carcinoma (HCC). MATERIAL AND METHODS Microarray data of GSE47786, including the 40 µM berberine-treated HepG2 human hepatoma cell line and 0.08% DMSO-treated as control cells samples, was downloaded from the GEO database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed; the protein-protein interaction (PPI) networks were constructed using STRING database and Cytoscape; the genetic alteration, neighboring genes networks, and survival analysis of hub genes were explored by cBio portal; and the expression of mRNA level of hub genes was obtained from the Oncomine databases. RESULTS A total of 56 upregulated and 8 downregulated DEGs were identified. The GO analysis results were significantly enriched in cell-cycle arrest, regulation of transcription, DNA-dependent, protein amino acid phosphorylation, cell cycle, and apoptosis. The KEGG pathway analysis showed that DEGs were enriched in MAPK signaling pathway, ErbB signaling pathway, and p53 signaling pathway. JUN, EGR1, MYC, and CDKN1A were identified as hub genes in PPI networks. The genetic alteration of hub genes was mainly concentrated in amplification. TP53, NDRG1, and MAPK15 were found in neighboring genes networks. Altered genes had worse overall survival and disease-free survival than unaltered genes. The expressions of EGR1, MYC, and CDKN1A were significantly increased, but expression of JUN was not, in the Roessler Liver datasets. CONCLUSIONS We found that JUN, EGR1, MYC, and CDKN1A might be used as diagnostic and therapeutic molecular biomarkers and broaden our understanding of the molecular mechanisms of HCC.

Exploration of miR-1202 and miR-196a in human endometrial cancer based on high throughout gene screening analysis.

Altered microRNA (miRNA) expression has been reported to participate in the pathogenesis of several human diseases, and particularly cancer. The present study examined the involvement of various miRNAs in the pathophysiology of endometrial cancer (EC) and atypical endometrial hyperplasia (AEH). We performed a high-throughput analysis of the miRNAs (miRNA microarray) found in samples of endometrial tissue obtained from 45 patients; among whom, 15 patients were diagnosed with EC, 15 patients were diagnosed with AEH, and the remainder were healthy donors. Next, we selected several miRNAs which exhibited at least a 2-fold difference in expression with a P<0.05 to validate these changes in 3 independent in vitro experiments that used real-time PCR analysis. Finally, miR-1202 and miR-196a were selected as target molecules whose effects on cell apoptosis, cell cycle changes, cell migratory and invasive abilities were investigated using flow cytometric and Transwell assays, respectively, after pre-treatment in vitro. After analyzing 125 miRNAs in a microarray assay, 6 miRNAs (3-high and 3-low expression) were further evaluated via paired comparison in all 3 groups. The validation test revealed a positive correlation between the microarray results and a high level of miR-1202 and a low level of miR-196a in the EC group, when compared with the AEH group. All of the data were normalized with data obtained from normal control donors. We found that either miR-1202 silencing or miR-196a overexpression affected AN3CA and HEC-1-A cells by increasing their apoptosis level and inducing G1 phase arrest while decreasing their migratory and invasive abilities. Inhibitors of miR-1202 and mimics of miR­196a may exert a protective effect, suggesting that miR-1202 and miR­196a may serve as biomarkers for evaluating the effectiveness of EC treatment.

Impact of communities, health, and emotional-related factors on smoking use: comparison of joint modeling of mean and dispersion and Bayes' hierarchical models on add health survey.

BACKGROUND: The analysis of correlated binary data is commonly addressed through the use of conditional models with random effects included in the systematic component as opposed to generalized estimating equations (GEE) models that addressed the random component. Since the joint distribution of the observations is usually unknown, the conditional distribution is a natural approach. Our objective was to compare the fit of different binary models for correlated data in Tabaco use. We advocate that the joint modeling of the mean and dispersion may be at times just as adequate. We assessed the ability of these models to account for the intraclass correlation. In so doing, we concentrated on fitting logistic regression models to address smoking behaviors. METHODS: Frequentist and Bayes' hierarchical models were used to predict conditional probabilities, and the joint modeling (GLM and GAM) models were used to predict marginal probabilities. These models were fitted to National Longitudinal Study of Adolescent to Adult Health (Add Health) data for Tabaco use. RESULTS: We found that people were less likely to smoke if they had higher income, high school or higher education and religious. Individuals were more likely to smoke if they had abused drug or alcohol, spent more time on TV and video games, and been arrested. Moreover, individuals who drank alcohol early in life were more likely to be a regular smoker. Children who experienced mistreatment from their parents were more likely to use Tabaco regularly. CONCLUSIONS: The joint modeling of the mean and dispersion models offered a flexible and meaningful method of addressing the intraclass correlation. They do not require one to identify random effects nor distinguish from one level of the hierarchy to the other. Moreover, once one can identify the significant random effects, one can obtain similar results to the random coefficient models. We found that the set of marginal models accounting for extravariation through the additional dispersion submodel produced similar results with regards to inferences and predictions. Moreover, both marginal and conditional models demonstrated similar predictive power.

Changes of gonadotropin-releasing hormone receptor 2 during the anadromous spawning migration in Coilia nasus.

BACKGROUND: An increase in the activity of the pituitary-gonad axis (PG-axis) and gonad development are essential for the onset of spawning migration in teleosts. In the fish Coilia nasus, gonad development and spawning migration up the Yangtze River occurs by the end of each summer. We hypothesized that gonadotropin releasing hormones receptor 2 (GnRH-R2), which together produce a signal that interacts with the PG-axis, may help to regulate spawning migration processes. RESULTS: In this regard, we (1) characterized the gonadosomatic index (GSI) in the anadromous fish C. nasus; (2) analyzed the GnRH-R2 mRNA expression levels in ovary and brain, and concentrations in the serum; and (3) identified the GnRH-R2 protein distribution in the brain and ovaries. We found strong relationships between all of these indices. CONCLUSIONS: The results indicate that GnRH-R2 could act together to promote spawning during the anadromous migration. There is some evidence that the GnRH-R2 gene expression levels and protein distributions change in association with the migratory behavior.

mTOR inhibition sensitizes ONC201-induced anti-colorectal cancer cell activity.

We here tested the anti-colorectal cancer (CRC) activity by a first-in-class small molecule TRAIL inducer ONC201. The potential effect of mTOR on ONC201's actions was also examined. ONC201 induced moderate cytotoxicity against CRC cell lines (HT-29, HCT-116 and DLD-1) and primary human CRC cells. Significantly, AZD-8055, a mTOR kinase inhibitor, sensitized ONC201-induced cytotoxicity in CRC cells. Meanwhile, ONC201-induced TRAIL/death receptor-5 (DR-5) expression, caspase-8 activation and CRC cell apoptosis were also potentiated with AZD-8055 co-treatment. Reversely, TRAIL sequestering antibody RIK-2 or the caspase-8 specific inhibitor z-IETD-fmk attenuated AZD-8055 plus ONC201-induced CRC cell death. Further, mTOR kinase-dead mutation (Asp-2338-Ala) or shRNA knockdown significantly sensitized ONC201's activity in CRC cells, leading to profound cell death and apoptosis. On the other hand, expression of a constitutively-active S6K1 (T389E) attenuated ONC201-induced CRC cell apoptosis. For the mechanism study, we showed that ONC201 blocked Akt, but only slightly inhibited mTOR in CRC cells. Co-treatment with AZD-8055 also concurrently blocked mTOR activation. These results suggest that mTOR could be a primary resistance factor of ONC201 in CRC cells.

miR-10b Inhibits Apoptosis and Promotes Proliferation and Invasion of Endometrial Cancer Cells via Targeting HOXB3.

MicroRNAs are small RNA that are tightly interrelated with the initiation, development, and metastasis of cancers. Studies have shown that miR-10b is increased in various cancers. However, the underlying mechanisms of miR-10b in the occurrence and metastasis of endometrial cancer are poorly understood. To investigate its roles and correlations with Homeobox box 3 (HOXB3) in endometrial cancer, cancer tissues and adjacent normal endometrium tissues from 20 patients with endometrial cancer were studied. miR-10b expression was significantly up-regulated (p < 0.01) in endometrial cancer tissue, whereas HOXB3 was lowly expressed. The silence of miR-10b resulted in significantly enhanced cell apoptosis, and remarkably reduced cell proliferation, migration, and invasion (p < 0.05). Moreover, the protein levels of HOXB3 were increased in KLE cells with silenced miR-10b, and dual-luciferase reporter assay suggested that miR-10b could directly target HOXB3. Furthermore, overexpression of HOXB3 promoted cell apoptosis but inhibited cell proliferation, migration, and invasion (p < 0.01). To conclude, miR-10b might control cell apoptosis, proliferation, migration, and invasion in endometrial cancer via regulation of HOXB3 expression.

The pharmacokinetic study of rutin in rat plasma based on an electrochemically reduced graphene oxide modified sensor.

An electrochemical method based on a directly electrochemically reduced graphene oxide (ERGO) film coated on a glassy carbon electrode (GCE) was developed for the rapid and convenient determination of rutin in plasma. ERGO was modified on the surface of GCE by one-step electro-deposition method. Electrochemical behavior of rutin on ERGO/GCE indicated that rutin underwent a surface-controlled quasi-reversible process and the electrochemical parameters such as charge transfer coefficient (α), electron transfer number (n) and electrode reaction standard rate constant (ks ) were 0.53, 2 and 3.4 s-1, respectively. The electrochemical sensor for rutin in plasma provided a wide linear response range of 4.70×10-7-1.25×10-5 M with the detection limit (s/n=3) of 1.84×10-8 M. The assay was successfully used to the pharmacokinetic study of rutin. The pharmacokinetic parameters such as elimination rate half-life (t1/2), area under curve (AUC), and plasma clearance (CL) were calculated to be 3.345±0.647 min, 5750±656.0 µg min/mL, and 5.891±0.458 mL/min/kg, respectively. The proposed method utilized a small sample volume of 10 µL and had no complicated sample pretreatment (without deproteinization), which was simple, eco-friendly, and time- and cost-efficient for rutin pharmacokinetic studies.

Kangiella profundi sp. nov., isolated from deep-sea sediment.

A taxonomic study employing a polyphasic approach was carried out on strain FT102(T), which was isolated from a deep-sea sediment sample collected in the south-west Indian Ocean at a depth of 2784 m. The strain was Gram-stain-negative, non-motile, rod-shaped and non-spore-forming. It grew optimally at 37-42 °C, pH 6.5-8.5 and in the presence of 1-4% (w/v) NaCl. Phylogenetic analysis of 16S rRNA gene sequences confirmed the separation of the novel strain from recognized members of the genus Kangiella that are available in public databases. Strain FT102(T) exhibited 95.5-98.6% 16S rRNA gene sequence similarity to the type strains of the eight recognized species of the genus Kangiella. The chemotaxonomically characteristic fatty acid iso-C15:0 and ubiquinone Q-8 were also detected. The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylmonomethylethanolamine. The DNA G + C content of strain FT102(T) was 45.0 mol%. The mean DNA-DNA relatedness values between strain FT102(T) and the type strains of Kangiella aquimarina and Kangiella koreensis were 47.3% and 13.7%, respectively. The combined results of phylogenetic, physiological and chemotaxonomic studies indicated that strain FT102(T) was affiliated with the genus Kangiella but differed from the recognized species of the genus Kangiella. Therefore, strain FT102T represents a novel species of the genus Kangiella, for which the name Kangiella profundi sp. nov. is proposed. The type strain is FT102(T) ( = CGMCC 1.12959(T) = KCTC 42297(T) = JCM 30232(T)).

NEDD4 ubiquitinates TRAF3 to promote CD40-mediated AKT activation.

CD40, a member of tumour necrosis factor receptor (TNFR) superfamily, has a pivotal role in B-cell-mediated immunity through various effector pathways including AKT kinase, but the signal transduction of CD40-meidated AKT activation is poorly understood. Here we report that the neural precursor cell expressed developmentally downregulated protein 4 (NEDD4), homologous to E6-AP Carboxyl Terminus family E3 ubiquitin ligase, is a novel component of the CD40 signalling complex. It has a key role in CD40-mediated AKT activation and is involved in modulating immunoglobulin class switch through regulating the expression of activation-induced cytidine deaminase. NEDD4 constitutively interacts with CD40 and mediates K63-linked ubiquitination of TNFR-associated factor3 (TRAF3). The ubiquitination of TRAF3 by NEDD4 is critical for CD40-mediated AKT activation. Thus, NEDD4 is a previously unknown component of the CD40 signalling complex necessary for AKT activation.