Blood cell characterization and transcriptome analysis reveal distinct immune response and host resistance of different ploidy cyprinid fish following Aeromonas hydrophila infection.

Aeromonas hydrophila can pose a great threat to survival of freshwater fish. In this study, A. hydrophila infection could decrease blood cell numbers, promote blood cell damage as well as alter the levels of alkaline phosphatase (ALP), lysozyme (LZM), aspartate aminotransferase (AST), total antioxidant capacity (T-AOC), total superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in immune-related tissues of red crucian carp (RCC, 2 N = 100) and triploid cyprinid fish (3 N fish, 3 N = 150). In addition, the significant alternation of antioxidant status was observed in PBMCs isolated from RCC and 3 N following LPS stimulation. The core differential expression genes (DEGs) involved in apoptosis, immunity, inflammation and cellular signals were co-expressed differentially in RCC and 3 N following A. hydrophila challenge. NOD-like receptor (NLR) signals appeared to play a critical role in A. hydrophila-infected fish. DEGs of NLR signals in RCCah vs RCCctl were enriched in caspase-1-dependent Interleukin-1ß (IL-1ß) secretion, interferon (IFN) signals as well as cytokine activation, while DEGs of NLR signals in 3Nah vs 3Nctl were enriched in caspase-1-dependent IL-1ß secretion and antibacterial autophagy. These results highlighted the differential signal regulation of different ploidy cyprinid fish to cope with bacterial infection.

A novel ferritin L (FerL) in hybrid crucian carp could participate in host defense against Aeromonas hydrophila infection and diminish inflammatory signals.

FerL, a multifunctional iron-storage polypeptide, not only exhibited a regulatory role in iron metabolism, but also participated in the regulation of fish immunity. In this study, ORF sequence of WR-FerL was 522 bp, encoding 173 amino acid residues. Tissue-specific analysis revealed that the highest expression of WR-FerL was detected in spleen. A. hydrophila challenge and LPS stimulation could sharply enhance WR-FerL mRNA expression in tissues and fish cells, respectively. Purified WR-FerL fusion peptide exhibited in vitro binding activity to A. hydrophila and endotoxin, limited bacterial dissemination to tissues as well as attenuated A. hydrophila-induced production of pro-inflammatory cytokines. Moreover, WR-FerL overexpression could abrogate NF-κB and TNFα promoter activity in fish cells. These results indicated that WR-FerL could play an important role in host defense against A. hydrophila infection.

Comparative analysis of erythrocyte hemolysis, plasma parameters and metabolic features in red crucian carp (Carassius auratus red var) and triploid hybrid fish following Aeromonas hydrophila challenge.

Aeromonas hydrophila can pose a great threat to survival of freshwater fish. In this study, A. hydrophila challenge could promote the erythrocyte hemolysis, increase free hemoglobin (FHB) level and generate malondialdehyde (MDA) production in plasma but decrease the levels of total antioxidant capacity (T-AOC), total superoxide dismutase (SOD), catalase (CAT), alkaline phosphatase (ALP) and lysozyme (LZM) of red crucian carp (RCC, 2 N = 100) and triploid hybrid fish (3 N fish, 3 N = 150) following A. hydrophila challenge. Elevated expression levels of heat shock protein 90 alpha (HSP90α), matrix metalloproteinase 9 (MMP-9), free fatty acid receptor 3 (FFAR3), paraoxonase 2 (PON2) and cytosolic phospholipase A2 (cPLA2) were observed in A. hydrophila-infected fish. In addition, A. hydrophila challenge could significantly increase expressions of cortisol, leucine, isoleucine, glutamate and polyunsaturated fatty acids (PUFAs) in RCC and 3 N, while glycolysis and tricarboxylic acid cycle appeared to be inactive. We identified differential fatty acid derivatives and their metabolic networks as crucial biomarkers from metabolic profiles of different ploidy cyprinid fish subjected to A. hydrophila infection. These results highlighted the comparative metabolic strategy of different ploidy cyprinid fish against bacterial infection.

Ferritin H can counteract inflammatory response in hybrid fish and its parental species after Aeromonas hydrophila infection.

Ferritin H can participate in the regulation of fish immunity. Tissue-specific analysis revealed that the highest expressions of Ferritin H in parental species were observed in spleen, while peaked level of Ferritin H mRNA in hybrid fish was observed in liver. In addition, A. hydrophila challenge could sharply enhance their Ferritin H mRNA expression in liver, kidney and spleen. To further investigate their roles in immune regulation, their Ferritin H fusion proteins were produced in vitro. Ferritin H fusion proteins could exhibit a direct binding activity to A. hydrophila and endotoxin in a dose-dependent manner, restrict dissemination of A. hydrophila to tissues and abrogate inflammatory cascades. Moreover, treatment with Ferritin H fusion proteins could reduce A. hydrophila-induced lipid peroxidation. These results indicated that Ferritin H in hybrid fish elicited a similar immune regulation of A. hydrophila-induced inflammatory signals in comparison with those of its parents.

Sustainable utilization of foundry waste: Forecasting mechanical properties of foundry sand based concrete using multi-expression programming.

Waste Foundry sand (WFS), a major solid waste from metal casting industry, is posing a significant environmental threat owing to its disposal to landfills. In this research, an innovative artificial intelligence technique i.e. Multi-Expression Programming (MEP) is applied to model the split tensile strength (ST) and modulus of elasticity (E) of concrete containing waste foundry sand (CWFS). The presented formulations correlate mechanical properties with four input variables i.e. w/c, foundry sand content, superplasticizer content and compressive strength. The results of statistical analysis validate the model accuracy as evident by the low values of objective function (0.033 for E and 0.052 for ST). Moreover, the average error in the predicted values is significantly low i.e. 0.287 MPa and 1.75 GPa for ST and E model, respectively. Parametric study depicts that the models are well trained to accurately predict the trends of mechanical properties with variation in mix parameters. The prediction models can promote the usage of WFS in green concrete thereby preventing waste disposal and contributing towards and sustainable construction.

Molecular mechanisms of mutualistic and antagonistic interactions in a plant-pollinator association.

Many insects metamorphose from antagonistic larvae into mutualistic adult pollinators, with reciprocal adaptation leading to specialized insect-plant associations. It remains unknown how such interactions are established at molecular level. Here we assemble high-quality genomes of a fig species, Ficus pumila var. pumila, and its specific pollinating wasp, Wiebesia pumilae. We combine multi-omics with validation experiments to reveal molecular mechanisms underlying this specialized interaction. In the plant, we identify the specific compound attracting pollinators and validate the function of several key genes regulating its biosynthesis. In the pollinator, we find a highly reduced number of odorant-binding protein genes and an odorant-binding protein mainly binding the attractant. During antagonistic interaction, we find similar chemical profiles and turnovers throughout the development of galled ovules and seeds, and a significant contraction of detoxification-related gene families in the pollinator. Our study identifies some key genes bridging coevolved mutualists, establishing expectations for more diffuse insect-pollinator systems.

[A new quinoline alkaloid from Scolopendra subspinipes mutilans].

Three compounds, including scolosprine C(1), uracil(2) and hypoxanthine(3), were isolated and purified from the ethyl acetate fraction of centipede by silica gel normal-phase column chromatography, reversed-phase medium pressure preparation chromatography, and high-pressure semi-preparative HPLC. The structure was elucidated through a combination of spectroscopic analyses [such as nuclear magnetic resonance(NMR) and mass spectrometry(MS)] and literature review. Among them, compound 1 was a new quinoline alkaloid. In previous reports, we have described the isolation and structure elucidation of one new and two known quinoline alkaloids. In this paper, we would report the isolation and structure elucidation of scolosprine C in detail.

High ionic conduction, toughness and self-healing poly(ionic liquid)-based electrolytes enabled by synergy between flexible units and counteranions.

Polymer electrolytes offer great potential for emerging wearable electronics. However, the development of a polymer electrolyte that has high ionic conductivity, stretchability and security simultaneously is still a considerable challenge. Herein, we reported an effective approach for fabricating high-performance poly(ionic liquids) (PILs) copolymer (denoted as PIL-BA) electrolytes by the interaction between flexible units (butyl acrylate) and counteranions. The introduction of butyl acrylate units and bis(trifluoromethane-sulfonyl)imide (TFSI-) counteranions can significantly enhance the mobility of polymer chains, resulting in the effective improvement of ion transport, toughness and self-healability. As a result, the PIL-BA copolymer-based electrolytes containing TFSI- counterions achieved the highest ionic conductivity of 2.71 ± 0.17 mS cm-1, 1129% of that of a PIL homopolymer electrolyte containing Cl- counterions. Moreover, the PIL-BA copolymer-based electrolytes also exhibit ultrahigh tensile strain of 1762% and good self-healable capability. Such multifunctional polymer electrolytes can potentially be applied for safe and stable wearable electronics.

Chimeric ferritin H in hybrid crucian carp exhibits a similar down-regulation in lipopolysaccharide-induced NF-κB inflammatory signal in comparison with Carassius cuvieri and Carassius auratus red var.

Ferritin H can participate in the regulation of teleostean immunity. ORF sequences of RCC/WCC/WR-ferritin H were 609 bp, while WR-ferritin H gene possessed chimeric fragments or offspring-specific mutations. In order to elucidate regulation of immune-related signal transduction, three fibroblast-like cell lines derived from caudal fin of red crucian carp (RCC), white crucian carp (WCC) and their hybrid offspring (WR) were characterized and designated as RCCFCs, WCCFCs and WRFCs. A sharp increase of ferritin H mRNA was observed in RCCFCs, WCCFCs and WRFCs following lipopolysaccharide (LPS) challenge. Overexpression of RCC/WCC/WR-ferritin H can decrease MyD88-IRAK4 signal and antagonize NF-κB, TNFα promoter activity in RCCFCs, WCCFCs and WRFCs, respectively. These results indicated that ferritin H in hybrid offspring harbors highly-conserved domains with a close sequence similarity to those of its parents, playing a regulatory role in inflammatory signals.

Prediction of Chloride Distribution for Offshore Concrete Based on Statistical Analysis.

Chloride-induced corrosion is the main threat to the service life of concrete structures. In order to better investigate chloride distribution in offshore concrete, this study proposed a new prediction model based on statistical analysis as well as a large body of experimental results collected from various sources. A detailed discussion found that the key influential parameters, such as diffusion coefficient ( D ), surface chloride concentration ( C S ) and penetration depth ( x ) are all highly time-dependent. The exposure zone, water-cement ratio and service time were also considered as relevant factors. The proposed model is then validated by two alternative tests and the results suggest that it is feasible in predicting the chloride content and penetration depth of concrete structures in a marine environment under chloride attack.

Prediction of mechanical properties of green concrete incorporating waste foundry sand based on gene expression programming.

Waste foundry sand (WFS) is a major pollutant generated from metal casting foundries and is classified as a hazardous material due to the presence of organic and inorganic pollutants which can cause adverse environmental impact. In order to promote the re-utilization of WFS, gene expression programming (GEP) has been employed in this study to develop empirical models for prediction of mechanical properties of concrete made with WFS (CMWFS). An extensive and reliable database of mechanical properties of CMWFS is established through a comprehensive literature review. The database comprises of 234 compressive strength, 163 split tensile strength and 85 elastic modulus results. The four most influential parameters i.e. water-to-cement ratio, WFS percentage, WFS-to-cement content ratio and fineness modulus of WFS are considered as the input parameters for modelling. The mechanical properties can be estimated by the application of proposed simplified mathematical expressions. The performance of the models is assessed by conducting parametric analysis, applying statistical checks and comparing with regression models. The results reflected that the proposed models are accurate and possess a high generalization and prediction capability. The findings of this study can enhance the re-usage of WFS for development of green concrete leading to environmental protection and monetary benefits.

Correction: Hydrophobic silane coating films for the inhibition of water ingress into the nanometer pore of calcium silicate hydrate gels.

Correction for 'Hydrophobic silane coating films for the inhibition of water ingress into the nanometer pore of calcium silicate hydrate gels' by Jiao Yu et al., Phys. Chem. Chem. Phys., 2019, DOI: .

Transient Receptor Potential V Channels Are Essential for Glucose Sensing by Aldolase and AMPK.

Fructose-1,6-bisphosphate (FBP) aldolase links sensing of declining glucose availability to AMPK activation via the lysosomal pathway. However, how aldolase transmits lack of occupancy by FBP to AMPK activation remains unclear. Here, we show that FBP-unoccupied aldolase interacts with and inhibits endoplasmic reticulum (ER)-localized transient receptor potential channel subfamily V, inhibiting calcium release in low glucose. The decrease of calcium at contact sites between ER and lysosome renders the inhibited TRPV accessible to bind the lysosomal v-ATPase that then recruits AXIN:LKB1 to activate AMPK independently of AMP. Genetic depletion of TRPVs blocks glucose starvation-induced AMPK activation in cells and liver of mice, and in nematodes, indicative of physical requirement of TRPVs. Pharmacological inhibition of TRPVs activates AMPK and elevates NAD+ levels in aged muscles, rejuvenating the animals' running capacity. Our study elucidates that TRPVs relay the FBP-free status of aldolase to the reconfiguration of v-ATPase, leading to AMPK activation in low glucose.

Pygo2 Regulates Adiposity and Glucose Homeostasis via ß-Catenin-Axin2-GSK3ß Signaling Pathway.

Wnt/ß-catenin signaling plays a key role in regulating adipogenesis through indirectly inhibiting the expression of C/EBPα and peroxisome proliferator-activated receptor γ (PPARγ); however, the detailed molecular mechanism remains poorly understood. Moreover, the factor(s) that determines the Wnt/ß-catenin output level during adipogenesis is also not completely defined. In this study, we showed that Pygo2 exhibited a declined expression pattern during adipocyte differentiation, resulting in an attenuated Wnt/ß-catenin output level. The mechanism study indicated that Pygo2 inhibition led to the downregulation of Axin2, a constitutive Wnt target, in the cytoplasm. Consequently, Axin2-bound GSK3ß was released and translocated into the nucleus to phosphorylate C/EBPß and Snail, resulting in an increase in the DNA binding activity of C/EBPß and decreased protein stability of Snail, which subsequently activated the expression of C/EBPα and PPARγ. Consistent with this, embryonic fibroblasts from Pygo2-/- mice exhibited spontaneous adipocyte differentiation, and adipocyte precursor-specific Pygo2-deficient mice exhibited increased adiposity with decreased energy expenditure. We further showed impaired glucose tolerance and decreased systemic insulin sensitivity in Pygo2-deficient mice. Our study revealed an association between Pygo2 function and obesity or diabetes.

A study of the dosimetric characteristics between different fixed-field IMRT and VMAT in early-stage primary mediastinal B-cell lymphoma.

This analysis was designed to compare dosimetric parameters among different fixed-field intensity-modulated radiation therapy (IMRT) solutions and volumetric-modulated arc therapy (VMAT) to identify which can achieve the lowest risk of organs at risk (OARs) and treatment delivery efficiently. A total of 16 patients (8 male and 8 female) with early-stage primary mediastinal large B-cell lymphoma (PMBCL) were enrolled with planned gross tumor volume (PGTV) 45 Gy and planning target volume (PTV) 40 Gy. Four different plans were generated: 5-, 7, 9-field IMRT, and VMAT. The dose distributions for PGTV and PTV OARs (lungs, left ventricle, heart, thyroid gland, and breasts) were compared. The monitor units (MUs) and treatment delivery time were also evaluated. Mean conformity index (CI) and homogeneity index (HI) for PGTV in 5F-, 7F-, 9F-IMRT, and VMAT were 1.01 and 1.10, 1.01 and 1.10, 1.01 and 1.10, and 1.01 and 1.11 (p = 0.963 and 0.843), whereas these 2 indices for PTV were 1.04 and 1.22, 1.03 and 1.19, 1.03 and 1.17, and 1.08 and 1.14 (p = 0.964 and 0.969), respectively. Dmean (Gy), V4 (%), D50 (Gy), and D80 (Gy) to the left and right breasts increased by 0.7 Gy and 0.1 Gy, 6.8% and 7.7%, 0.9 Gy and 1.7 Gy, and 1.0 Gy and 1.5 Gy in VMAT, respectively. The 9-beam IMRT plan had the highest MUs (25,762.4 MUs) and the longest treatment delivery time (10.7 minutes); whereas, the VMAT had the lowest MUs (13,345.0) and the shortest treatment delivery time (5.9 minutes). Seven- and 9-field IMRT and VMAT provide improved tumor coverage compared with 5F-IMRT, whereas VMAT shows higher treatment delivery efficiency than IMRT technique. Seven- and 9-field IMRT slightly reduce the low dose radiation exposure of breasts compared with VMAT technique. The 7- and 9-field IMRT and VMAT techniques both can be safely and efficiently delivered to patients with PMBCL.

Polymorphisms of the stem cell marker gene CD133 are associated the clinical outcome in a cohort of Chinese non-small cell lung cancer patients.

OBJECTIVES: To evaluate the prognostic relevance of four functional single nucleotide polymorphisms (SNPs) in CD133 (rs2240688A>C, rs10022537T>A, rs7686732C>G, and rs3130C>T) on overall survival (OS) of non-small cell lung cancer (NSCLC) patients. DESIGN: Retrospective cohort study. SETTING: Department of General Surgery, in a general hospital, Henan Province, China. PARTICIPANTS: NSCLC patients aged ≥18 years, who were not receiving preoperative neoadjuvant therapies and had a blood sample available for genotyping, were eligible for inclusion. Those participants who were pregnant or breastfeeding, had a previous history of cancer, had other primary tumours, or who had had primary tumours of the skin and nasopharynx, were excluded from the study. OUTCOME MEASURES: The primary endpoint was OS, which was calculated from the date of enrolment until the date of death or date of last follow-up. RESULTS: There was a total of 1383 participants, with a median age of 63 years; 726 (52.5%) were male. Compared with thers2240688 AA genotype, the variant AC/CC genotypes were independently associated with OS (HR 1.27, 95% CI 1.12 to 1.45 for AC genotype; HR 2.32, 95% CI 1.91 to 2.80 for CC genotype). Higher hazard ratios for associations between CD133 rs2240688 polymorphism and OS were observed in patients with adjuvant chemotherapy (HR 1.86, 95% CI 1.52 to 2.26) and radiotherapy for curative intent (HR 1.90, 95% CI 1.55 to 2.33). CONCLUSIONS: The study confirmed the significant association between the SNP rs2240688 A>C of CD133 and OS of NSCLC patients. Larger population-based studies in different ethnic groups are necessary to further validate the role and mechanisms of CD133 in NSCLC.

OVOL2 antagonizes TGF-ß signaling to regulate epithelial to mesenchymal transition during mammary tumor metastasis.

Great progress has been achieved in the study of the role of TGF-ß signaling in triggering epithelial-mesenchymal transition (EMT) in a variety of cancers; however, the regulation of TGF-ß signaling during EMT in mammary tumor metastasis has not been completely defined. In the present study, we demonstrated that OVOL2, a zinc finger transcription factor, inhibits TGF-ß signaling-induced EMT in mouse and human mammary tumor cells, as well as in mouse tumor models. Data from the Oncomine databases indicated a strong negative relationship between OVOL2 expression and breast cancer progression. Moreover, our experiments revealed that OVOL2 inhibits TGF-ß signaling at multiple levels, including inhibiting Smad4 mRNA expression and inducing Smad7 mRNA expression, blocking the binding between Smad4 and target DNA, and interfering with complex formation between Smad4 and Smad2/3. These findings reveal a novel mechanism that controls the TGF-ß signaling output level in vitro and in vivo. The modulation of these molecular processes may represent a strategy for inhibiting breast cancer invasion by restoring OVOL2 expression.

Yes-associated protein/TEA domain family member and hepatocyte nuclear factor 4-alpha (HNF4α) repress reciprocally to regulate hepatocarcinogenesis in rats and mice.

Great progress has been achieved in the study of Hippo signaling in regulating tumorigenesis; however, the downstream molecular events that mediate this process have not been completely defined. Moreover, regulation of Hippo signaling during tumorigenesis in hepatocellular carcinoma (HCC) remains largely unknown. In the present study, we systematically investigated the relationship between Yes-associated protein/TEA domain family member (YAP-TEAD) and hepatocyte nuclear factor 4-alpha (HNF4α) in the hepatocarcinogenesis of HCC cells. Our results indicated that HNF4α expression was negatively regulated by YAP1 in HCC cells by a ubiquitin proteasome pathway. By contrast, HNF4α was found to directly associate with TEAD4 to compete with YAP1 for binding to TEAD4, thus inhibiting the transcriptional activity of YAP-TEAD and expression of their target genes. Moreover, overexpression of HNF4α was found to significantly compromise YAP-TEAD-induced HCC cell proliferation and stem cell expansion. Finally, we documented the regulatory mechanism between YAP-TEAD and HNF4α in rat and mouse tumor models, which confirmed our in vitro results. CONCLUSION: There is a double-negative feedback mechanism that controls TEAD-YAP and HNF4α expression in vitro and in vivo, thereby regulating cellular proliferation and differentiation. Given that YAP acts as a dominant oncogene in HCC and plays a crucial role in stem cell homeostasis and tissue regeneration, manipulating the interaction between YAP, TEADs, and HNF4α may provide a new approach for HCC treatment and regenerative medicine. (Hepatology 2017;65:1206-1221).

Patterns of Primary Tumor Invasion and Regional Lymph Node Spread Based on Magnetic Resonance Imaging in Early-Stage Nasal NK/T-cell Lymphoma: Implications for Clinical Target Volume Definition and Prognostic Significance.

PURPOSE: This study aimed to determine the pathways of primary tumor invasion (PTI) and regional lymph node (LN) spread based on magnetic resonance imaging (MRI) in early-stage nasal NK/T-cell lymphoma (NKTCL), to improve clinical target volume (CTV) delineation and evaluate the prognostic value of locoregional extension patterns. METHODS AND MATERIALS: A total of 105 patients with newly diagnosed early-stage nasal NKTCL who underwent pretreatment MRI were retrospectively reviewed. All patients received radiation therapy with or without chemotherapy. RESULTS: The incidences of PTI and regional LN involvement were 64.7% and 25.7%, respectively. Based on the incidence of PTI, involved sites surrounding the nasal cavity were classified into 3 risk subgroups: high-risk (>20%), intermediate-risk (5%-20%), and low-risk (<5%). The most frequently involved site was the nasopharynx (35.2%), followed by the maxillary (21.9%) and ethmoid (21.9%) sinuses. Local disease and regional LN spread followed an orderly pattern without LN skipping. The retropharyngeal nodes (RPNs) were most frequently involved (19.0%), followed by level II (11.4%). The 5-year overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) rates for all patients were 72.8%, 65.2%, and 90.0%, respectively. The presence of PTI and regional LN involvement based on MRI significantly and negatively affected PFS and OS. CONCLUSIONS: Early-stage nasal NKTCL presents with a high incidence of PTI but a relatively low incidence of regional LN spread. Locoregional spread followed an orderly pattern, and PTI and regional LN spread are powerful prognostic factors for poorer survival outcomes. CTV reduction may be feasible for selected patients.