Search

Low-dielectric constant polymers are widely used in various microelectronic materials. With the development of 5G communication technology, there is an urgent need for polymer materials with low dielectric constant at high frequency, good thermal resistance, and mechanical properties. In this study, four novel poly (aryl ether ketone) (PAEK) containing different numbers of methylene groups were synthesized via nucleophilic polycondensation reaction. At 10 GHz, these polymer films exhibit excellent dielectric properties with dielectric constants as low as 2.76. The relationship between the dielectric constant and the number of methylene groups is illustrated by constructing the amorphous accumulation cell model. In addition, methylene groups provided the polymer with favorable mechanical performance, including Young's modulus in the range of 2.17–2.21 GPa, the tensile strength from 82.0 to 88.5 MPa and the elongation at the break achieved 7.94%, respectively. Simultaneously, the polymer maintains good thermal resistance with a glass transition temperature (Tg) reaching 216 °C. The result indicates that the obtained novel PAEK is potentially valuable in the field of high-frequency communications. [ABSTRACT FROM AUTHOR]

Multilevel boost converter is a multi-input multi-output nonlinear strongly coupled system. There is a coupling relationship between flying capacitor voltages and output voltage. In this paper, an optimal control method for n + 1-level boost converter based on exact feedback linearization and decoupling is proposed. The flying capacitor voltages and energy function are selected as the output functions to linearize and decouple the original system into n − 1 first-order subsystems and a second-order subsystem. Based on the optimal control theory, flying capacitor voltage balancing controllers are designed for n − 1 first-order subsystems, and an output voltage regulating controller is designed for the second-order subsystem. A five-level boost converter control system is verified by numerical simulation and a three-level boost converter control system is verified by experiment. Simulation and experimental results show that the proposed control strategy has better dynamic regulation performance and stronger robustness than PI decoupling control strategy based on small-signal model. [ABSTRACT FROM AUTHOR]

The lysin motif (LysM)-containing protein is one of widespread pattern-recognition receptors in prokaryotes and eukaryotes. Numerous LysM-containing gene sequences are present in gene databases; however, few have been well characterized, especially in echinoderms. In this study, the full-length cDNA of a novel LysM-containing gene was obtained from the sea cucumber Apostichopus japonicus , named AjLysM-1 , using polymerase chain reaction (PCR) combined with rapid amplification of cDNA ends. We prepared and expressed recombinant AjLysM-1 protein (rAjLysM-1) and determined its pathogen-recognition ability by enzyme-linked immunosorbent and immunofluorescence assays. We also analyzed the tissue expression pattern and response to immune challenges of AjLysM-1 using quantitative real-time reverse transcription-PCR and in situ hybridization. The AjLysM-1 protein was predicted to be an intracellular non-secreted LysM-containing protein, highly homologous to the same protein in other marine echinoderms. AjLysM-1 transcripts were highest expressed in coelomocytes and were strikingly induced by challenge with representative bacterial and fungal polysaccharides. rAjLysM-1 showed weak binding to mannan, Pseudoalteromonas nigrifaciens , and Shewanella baltica , implying that AjLysM-1 might provide inadequate defense against Gram-negative bacteria and fungi. Notably, rAjLysM-1 also interacted with tyrosine protein kinase and filamin-B, indicating that it could be involved in focal adhesion in A. japonicus. These findings improve our understanding of the functions of LysM-containing proteins in marine echinoderms. • A novel LysM-containing gene in Apostichopus japonicus , AjLysM-1 , were uncovered. • AjLysM-1 is an intracellular non-secreted protein with pathogen-recognition abilities. • AjLysM-1 might provide inadequate defense against Gram-negative bacteria and fungi. • AjLysM-1 was proven to be interacted with tyrosine protein kinase and filamin-B. [ABSTRACT FROM AUTHOR]

Summary: Nowadays, the true economic and nutritional value of food is underpinned by both origin and quality traits, more often expressed as increased quality benefits derived from the origin source. Gut microbiota contribute to food metabolism and host health, therefore, it may be suitable as a qualifying indicator of origin and quality of economic species. Here, we investigated relationships between the gut microbiota of the sea cucumber (Apostichopus japonicus), a valuable aquaculture species in Asia, with their origins and quality metrics. Based on data from 287 intestinal samples, we generated the first biogeographical patterns for A. japonicus gut microbiota from origins across China. Importantly, A. japonicus origins were predicted using the random forest model that was constructed using 20 key gut bacterial genera, with 97.6% accuracy. Furthermore, quality traits such as saponin, fat and taurine were also successfully predicted by random forest models based on gut microbiota, with approximately 80% consistency between predicted and true values. We showed that substantial variations existed in the gut microbiota and quality variables in A. japonicus across different origins, and we also demonstrated the great potential of gut microbiota to track A. japonicus origins and predict their quality traits. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) are an important family of proteinases involved in various physiological processes and associated with the immune response. However, the role of MMPs in the immune response remains unclear. To explore the possible role of MMPs in innate immunity, this study selected the MMP-16 gene encoding peptidoglycan (PGN) binding domain identified in the sea cucumber Apostichopus japonicus (named AjMMP-16, GenBank accession No. AQT26486) for microbial polysaccharide-induced transcriptional expression analysis by quantitative real-time PCR, correlation analysis with nine representative genes from A. japonicus immune pathways in microbial polysaccharide-induced transcriptional expression by using Pearson's correlation test, and prokaryotic recombinant expression. Next, its recombinant protein was employed for microbial polysaccharide-binding analysis with ELISA and bacterial binding analysis with the indirect immunofluorescence method. The results showed that AjMMP-16 was significantly induced by diaminopimelic acid (DAP)-type PGN, lipopolysaccharide, mannan, and β-1,3-glucan and was closely correlated with myeloid differentiation factor 88 (MyD88) in microbial polysaccharide-induced transcriptional expression. In addition, recombinant AjMMP-16 bound to lysine-type PGN, DAP-type PGN, lipopolysaccharide, mannan, β-1,3-glucan, Vibrio splendidus , Pseudoalteromonas nigrifaciens , Shewanella baltica , Bacillus cereus , Escherichia coli , and Staphylococcus aureus. These results suggest that AjMMP-16 might act as a pattern recognition receptor in innate immunity and play an important role in initiating the MyD88-dependent Toll-like receptor signaling pathway. • AjMMP-16 was able to be induced by diverse microbial polysaccharides. • AjMMP-16 might be associated with MyD88-dependent TLR signaling pathway. • AjMMP-16 had broad-spectrum pathogen recognition ability. [ABSTRACT FROM AUTHOR]

Effects of dietary Lactobacillus acidophilus and tussah immunoreactive substances (TIS) on disease resistance of sea cucumber (Apostichopus japonicus) against Vibrio splendidus were investigated. Sea cucumbers were fed with a basal diet in the control group (CK group) or were supplemented with L. acidophilus (L group), TIS (T group) or both (LT group). The challenge test with V. splendidus was conducted after the feeding trial. The cumulative mortality rate in the LT group was significantly lower, while the highest mortality occurred in the control group. The LT group showed better digestive and immune parameters compared with the other treatments. Dietary L. acidophilus and TIS in combination could effectively enhance digestive function and food uptake, depress oxidative damage and improve the organismal defence capability. Regarding gut microbiota profiles, the LT group was more capable of inhibiting potentially opportunistic pathogens and regulating intestinal flora balance compared with the other groups. The administration of L. acidophilus and TIS in the diet could effectively improve disease resistance against V. splendidus of sea cucumbers by improving the immune and digestive enzyme activities and modulating intestinal microflora, signalling a potential role in the development and production of aquatic feed. [ABSTRACT FROM AUTHOR]

9,9-bis(4-hydroxyphenyl)fluorene (BPF) is a highly structurally symmetric bisphenol with excellent optical properties of low birefringence and high refractive index, however, the glass transition temperature (T g) of its polyester is high (T g>300°C), which makes it difficult to be thermally processed and limits its application. On the other hand, 4,4′-Thiobis (2-methylphenol) (T2MP) has a flexible thioether group, its introduction not only brings high refractive index, but also can appropriately reduce the T g of the polymer. Therefore, by combining the advantages of both of them, we prepared aromatic polyesters with high refractive index and stabilization. This study provides a route that can appropriately reduce T g without loss of refractive index. [ABSTRACT FROM AUTHOR]

Pattern recognition receptors (PRRs) are the first line of immune defense in invertebrates against pathogen infection; they recognize pathogens and transmit signals to downstream immune pathways. Among these, peptidoglycan recognition proteins (PGRPs) are an important family in invertebrates that generally comprise of complicated isoforms. A comprehensive understanding of PGRPs in evolutionarily and economically important marine invertebrates, such as the sea cucumber, Apostichopus japonicus, is crucial. Previous studies have identified two PGRPs in sea cucumber, AjPGRP-S and AjPGRP-S1 , and another novel short-type PGRP, AjPGRP-S3 , was additionally identified here. The full-length cDNA sequence of AjPGRP-S3 was obtained here by PCR-RACE, followed by which showed its gene expression analyses by in situ hybridization that showed it to be relatively highly expressed in coelomocytes and tube feet. Based on an analysis of the recombinant protein, rAjPGRP-S3, a board-spectrum pathogen recognition ability was noted that covered diverse Gram-negative and -positive bacteria, and fungi. Moreover, according to the results of yeast two-hybridization, it was suggested that rAJPGRP-S3 interacted with multiple immune-related factors, including proteins involved in the complement system, extracellular matrix, vesicle trafficking, and antioxidant system. These findings prove the important functions of AjPGRP-S3 in the transduction of pathogen signals to downstream immune effectors and help explore the functional differences in the AjPGRP isoforms. • A novel short-type peptidoglycan recognition gene in sea cucumber, AjPGRP-S3 , were uncovered. • AjPGRP-S3 is strongly expressed in coelomocytes with unique polysaccharide recognition specificity. • AjPGRP-S3 interacts with complement system and extracellular matrix proteins. • AjPGRP-S3 transduces the pathogen invasion-related signal to activate phagocytosis. [ABSTRACT FROM AUTHOR]

The arcuate nucleus of the hypothalamus (ARC) plays a key role in linking peripheral metabolic status to the brain melanocortin system, which influences a wide range of physiological processes including the sympathetic nervous system and blood pressure. The importance of the activity of agouti-related peptide (AgRP)- and proopiomelanocortin (POMC)-expressing neurons, two molecularly distinct populations of ARC neurons, for metabolic regulation is well established, but their relevance for sympathetic and cardiovascular control remains unclear. We used designer receptors exclusively activated by designer drug (DREADD) technology to study how activation of AgRP and POMC neurons affect renal sympathetic nerve traffic and blood pressure. In addition to the drastic feeding-stimulatory effect, DREADD-mediated activation of AgRP, but not POMC neurons, induced an acute reduction in renal sympathetic nerve activity in conscious mice. Paradoxically, however, DREADD-mediated chronic activation of AgRP neurons caused a significant increase in blood pressure specifically in the inactive light phase. On the other hand, chronic activation of POMC neurons led to a significant reduction in blood pressure. These results bring new insights to a previously unappreciated role of ARC AgRP and POMC neuronal activity in autonomic and cardiovascular regulation. NEW & NOTEWORTHY Agouti-related peptide (AgRP)- and proopiomelanocortin (POMC)-expressing neurons of the arcuate nucleus are essential components of the brain melanocortin system that controls various physiological processes. Here, we tested the metabolic and cardiovascular effects of direct activation of these two populations of neurons. Our findings show that, in addition to stimulation of food intake, chemogenetic mediated activation of hypothalamic arcuate nucleus AgRP, but not POMC, neurons reduce renal sympathetic traffic. Despite this, chronic activation of AgRP neurons increased blood pressure. However, chronic activation of POMC neurons led to a significant reduction in blood pressure. Our findings highlight the importance of arcuate nucleus AgRP and POMC neuronal activity in autonomic and cardiovascular regulation. [ABSTRACT FROM AUTHOR]

Sea cucumber Apostichopus japonicus is an important economic species in echinoderms; however, its culture frequently suffered from diseases. Environmental stress was found to be a dominant inducer of A. japonicus diseases, and thus, discovering the characteristics of immune system under environmental stress is of great significance for disease control in A. japonicus culture. Phenoloxidase (PO) is recognized as a crucial immune‐related enzyme in invertebrates. In order to preliminarily illustrate the different roles that A. japonicus PO isoforms play under environmental stresses, the transcriptional expression of three identified A. japonicus PO isoforms (named as AjPOI, AjPOII and AjPOIII respectively) after different in vivo environmental stress simulations was determined with quantitative real‐time PCR method. Meanwhile, the transcriptional expression analysis of other representational immune‐related factors under environmental stresses was also performed for the evaluation of relationships between AjPOs and other immune‐related factors. The correlations between AjPOs and other immune‐related factors were analysed using Pearson correlation coefficient, and the effects of AjPOs on other immune‐related factors were then tested by dsRNA interference method. The results of transcriptional expression analysis indicated that AjPOI was involved in the resistance to low salinity, low temperature and hypoxia; AjPOII and AjPOIII were both required for the resistance to low salinity, high temperature, low temperature and hypoxia; and all three AjPOs were excluded from the response against high salinity. In addition, three AjPOs were found to take part in different periods of resistance to environmental stresses, and this property made A. japonicus PO system capable of outputting resistance activities continuously. The correlation analysis combined with dsRNA interference test revealed that AjPOI was capable of regulating AjCTSD, AjI‐LYZ and AjMTF expression; AjPOII and AjPOIII both played important roles in the regulation of AjC‐LYZ expression; and AjPOIII was also able to regulate AjToll expression. These findings suggested that A. japonicus PO isoforms function in innate immunity not only via catalysing the oxidative reactions, but also by broadly regulating the expression of other immune‐related factors. On the whole, three AjPOs showed obvious differences among each other in the resistance to environmental stresses and the regulation of other immune‐related factors, but comparatively, AjPOII and AjPOIII shared more similarity. [ABSTRACT FROM AUTHOR]

To investigate the promoting effects and mechanisms of low intensity pulsed ultrasound (LIPUS) on the migration of bone marrow-derived mesenchymal stem cells (BMSCs). The BMSCs migration was researched from cell and animal experiments. In the cell experiment, the BMSCs was treated using LIPUS (30 mW/cm2, 20 min/day, 2 days), and the wound healing and transwell migration were observed. In the animal experiment, the BMSCs labelled with green fluorescent protein (GFP) were injected into rats with femoral defects via the tail vein (1 × 106/mL). The healing of bone was detected using x-ray and sampled for hematoxylin & eosin (H&E) staining and fluorescence microscopy. About the mechanisms, the cellular F-actin of cytoskeleton was stained with FITC-phalloidin. The changes of BMSCs genes after LIPUS treatment were screened using microarray assay and verified using quantitative real-time polymerase chain reaction (qRT-PCR). The biological processes of those genes were predicted by KEGG analysis. The protein expression levels of FAK, ERK1/2 and myosin II related migration were detected using western blotting. The results showed LIPUS promoted the BMSCs migration (p <.05) without significant temperature changes (p >.05) in vitro and in vivo than control group (p <.05). The cytoskeletal rearrangement was carried out, and the ITGA8 gene related with cell migration was found with high expression after LIPUS treatment (p <.05). FAK inhibitor (PF-573228) and ERK1/2 inhibitor (U0126) were proved, in turn, decreased the BMSCs migration induced using LIPUS (p <.05). LIPUS can promote the BMSCs migration in vitro and in vivo, one mechanism may be related to the activation of FAK-ERK1/2 signalling pathways using LIPUS.Experiments in vivo and in vitro were designed to explore the migration and mechanisms of BMSCs treated using LIPUS. [ABSTRACT FROM AUTHOR]

• A series of novel poly (aryl ether sulfone) (ABPFx) were successfully synthesized. • ABPFx membrane exhibits high gas separation performance for H 2 /N 2. • ABPFx has excellent thermal resistance with the T g reaching 277 °C. A series of poly (aryl ether sulfone) containing different contents of amino groups (ABPFx) were synthesized by nucleophilic polycondensation reaction. The ABPFx has excellent thermal resistance with the T g reaching 277 °C as well as maintains good mechanical and film-forming properties. Particularly, the ABPF10 membrane exhibits high gas permeability [P (H 2) = 22.24 Bar] and gas selectivity [α (H 2 /N 2) = 63.5]. Consequently, the ABPFx membranes have potential application value in the field of gas separation for hydrogen separation. [ABSTRACT FROM AUTHOR]

The gender differences of immunity have been elucidated in many vertebrates and invertebrates. However, the information of this difference was still not clear in the sea cucumber Apostichopus japonicus , which is one of the most valuable aquaculture species and susceptible to diseases caused by pathogen infection. In the present study, the transcriptome of coelomocytes from female and male A. japonicus before and after spawning was obtained by RNA-sequencing technology. A total of 4,538 and 8,248 differentially expressed genes were identified between female and male A. japonicus before and after spawning, respectively, indicating that the gender differences of gene expression profiles in A. japonicus were more remarkable after spawning. Further KEGG enrichment analyses were conducted for both male and female up-regulated genes before and after spawning. The results revealed that the capacity to kill pathogens in female A. japonicus might be more powerful than that in males no matter before and after spawning; the antioxidant ability in male A. japonicus was probably stronger than that in females after spawning; the complement system in male A. japonicus might be more effective than that in females after spawning; and the apoptosis was likely to be more serious in male A. japonicus before spawning. Moreover, we speculated that the fatty acid composition might be one of the inducements for gender specific immune differences of A. japonicus. Overall, the results of our study illustrated the global gender specific immune differences of A. japonicus and contributed to understanding of the molecular mechanisms underlying sea cucumber immune regulation. • Differentially expressed genes related to gender were analyzed in Apostichopus japonicus. • The capacity to kill pathogen was probably more powerful in female A. japonicus. • The antioxidant ability might be stronger in male A. japonicus after spawning. • The complement system is more effective in male A. japonicus after spawning. • The apoptosis was likely more serious in male A. japonicus before spawning. [ABSTRACT FROM AUTHOR]

This paper presents a multi-objective optimization methodology that applies the Non-dominated Sorting Genetic Algorithm-II(NSGA-II) to propeller design, and realizes Fluid-Structure Interaction (FSI) weak-coupling based on Panel Method (PM) and the Finite Element Method (FEM). The FSI iterative process and the convergent pressure coefficient distribution and pressure fluctuation of HSP (a propeller installed on a Japanese bulk freighter - Seiun-Maru) are numerical calculated. The FSI results turn out to have higher precision than those without FSI. The appropriate optimization parameters are chosen after studying five cases. The Sobol method, a global Sensitivity Analysis (SA) algorithm, is used to quantify the dependence of objectives and constraints on the input parameters. In the multi-objective optimization methodology, efficiency, unsteady force, and mass are chosen as optimum objectives under certain constraints. Effectiveness and robustness of the methodology are validated by running the program starting from four different random values, which all improve the objectives and converge to the similar results. The proposed multi-objective optimization methodology could be a promising tool for propeller design to help improve design efficiency and ability in the future. [ABSTRACT FROM AUTHOR]

Abstract: The monocytic MDSC (M‐MDSC) is one of the major types of MDSCs, which play important roles in suppression of antitumor immunity. However, the mechanisms underlying how M‐MDSCs so heavily accumulate in patients with cancer are still poorly understood. The purpose of this study was to identify miRNAs that regulate the proliferation and differentiation of M‐MDSCs. Microarray analysis was performed to identify differentially expressed miRNAs between tumor‐induced M‐MDSCs (TM‐MDSCs) and their counterparts from tumor‐free mice. The miRNAs and their target genes that regulate the proliferation and differentiation of myeloid cells were predicted by bioinformatics analysis and validated by RT‐qPCR. Luciferase reporter assays were used to analyze the relationships between miRNAs and target genes. Overexpression of candidate miRNAs and target genes in myeloid cells was conducted to verify their functions in cell proliferation, differentiation, and apoptosis. Our data showed that miR‐486 was overexpressed in TM‐MDSCs. Cebpa was predicted to be one of the target genes of miR‐486 that regulates the proliferation of myeloid cells. Expression of Cebpa was inversely correlated with miR‐486 in TM‐MDSCs, and we found that overexpression of miR‐486 suppressed the expression of Cebpa in both 293T cells determined by luciferase reporter assays and in myeloid cells determined by RT‐qPCR. Overexpression of miR‐486 promoted proliferation and suppressed apoptosis in myeloid cells, as opposed to overexpression of Cebpa, which promoted the opposing phenotype. Overexpression of either miR‐486 or Cebpa inhibited differentiation of myeloid cells. This study indicates that miR‐486 promotes proliferation and suppresses apoptosis in myeloid cells by targeting Cebpa in vitro, suggesting that miR‐486 and Cebpa might be involved in the expansion of TM‐MDSCs in tumor‐bearing mice. [ABSTRACT FROM AUTHOR]

Salinity is an important environmental factor in microbial ecology for affecting the microbial communities in diverse environments. Understanding the salinity adaptation mechanisms of a microbial community is a significant issue, while most previous studies only covered a narrow salinity range. Here, variations in seawater prokaryotic communities during the whole salt drying progression (salinity from 3% to 25%) were investigated. According to high‐throughput sequencing results, the diversity, composition, and function of seawater prokaryotic communities varied significantly along the salinity gradient, expressing as decreased diversity, enrichment of some halophilic archaea, and powerful nitrate reduction in samples with high salt concentrations. More importantly, a sudden and dramatic alteration of prokaryotic communities was observed when salinity reached 16%, which was recognized as the change point. Combined with the results of network analysis, we found the increasing of complexity but decreasing of stability in prokaryotic communities when salinity exceeded the change point. Moreover, prokaryotic communities became more deterministic when salinity exceeded the change point due to the niche adaptation of halophilic species. Our study showed that substantial variations in seawater prokaryotic communities along an extremely wide salinity gradient, and also explored the underlying mechanisms regulating these changes. [ABSTRACT FROM AUTHOR]

Apostichopus japonicus is one of the most important aquaculture species in China. Skin ulceration syndrome (SUS) of sea cucumber is a common and serious disease affected the development of A . japonicus culture industry. To better understand the response mechanisms of A . japonicus during SUS progression, the protein variations in the body wall of A . japonicus at different stages of SUS were investigated by a comparative proteomic approach based on isobaric tags for relative and absolute quantification. A total of 1449 proteins were identified from the samples at different SUS stages. Among these proteins, 145 proteins were differentially expressed in the SUS-related samples compared to those of healthy A . japonicus . These differentially expressed proteins involved a wide range of functions. Among these differentially expressed proteins, only two proteins, alpha-5-collagen and an unknown function protein, were differentially expressed during the whole progression of SUS compared with healthy A . japonicus . In addition, ATP synthase subunit beta (ATP5β) interacted with a variety of proteins with different functions during the SUS progression. These results implied that alpha-5-collagen and ATP5β could play important roles during the SUS progression of A . japonicus . Our study provided a new sight to understand the molecular responses of sea cucumber during the SUS progression and accumulated data for the prevention of SUS in sea cucumber aquaculture. Biological significance The current study aimed to reveal how the body wall of Apostichopus japonicus response to skin ulceration syndrome (SUS). To the best of our knowledge, this is the first proteomic study analyzing the differences in protein profile of sea cucumber during the whole SUS progression. By analyzing the expression differences of the proteome via isobaric labeling-based quantitative proteomic, we identified some proteins which may play important roles during the SUS progression. According to the enrichment analyses of these proteins based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, a draft view of how the sea cucumber affected by SUS has been drawn. The common and unique differentially expressed proteins by Venn analysis showed that alpha-5-collagen was down-regulated at all stages of SUS, which had the potential as a target component for the host-directed SUS therapy. In addition, ATP5β, a subunit of mitochondrial ATP synthase, interacting with a variety of proteins with different functions during the SUS progression. This result illustrated that energy production and metabolism could play an important role in the formation of skin ulceration and resistance to pathogens in sea cucumber. The results of this study will be helpful for researchers to gain insights into the complex molecular mechanism of SUS in sea cucumber. [ABSTRACT FROM AUTHOR]

In order to preliminarily explore the joint involvement of different immune-related factors during the same immune process in Apostichopus japonicus , the transcriptional expression of Cu/Zn superoxide dismutase (Cu/Zn-SOD), catalase (CAT), c-type lysozyme (c-LYZ), i-type lysozyme (i-LYZ), cathepsin D, melanotransferrin (MTF), Toll, c-type lectin (c-LCT) and complement 3 (C3) during the development from fertilized eggs to juveniles and after challenging the juveniles with Vibrio splendidus , Pseudoalteromonas nigrifaciens , Shewanella baltica and Bacillus cereus , respectively, was measured using the method of quantitative real-time PCR (qRT-PCR), and then the correlations among different immune-related factors were analyzed. The results showed that the selected immune-related factors were expressed at all of the determined developmental stages and significantly up-regulated at doliolaria stage, suggesting the selected factors are indispensable immune components and the immune system might be broadly activated at doliolaria stage in A. japonicus . After challenged with four pathogenic bacteria, Cu/Zn-SOD, CAT, i-LYZ, cathepsin D, MTF, Toll, C3 were all significantly down-regulated at 4 h, indicating that some components of A. japonicus immune system might be inhibited at the beginning of pathogenic bacteria invasion. The immune-responsive analysis also showed that the significant regulation in Toll after challenged with four tested bacteria, that in MTF after challenged with S. baltica and that in C3 after challenged with P. nigrifaciens were all minus, suggesting Toll, MTF and C3 are probably the primary targets of pathogenic bacteria attack. Furthermore, the correlation analysis indicated that, all of the selected immune-related factors except cathepsin D might be in the same immune regulatory network during A. japonicus development, while all of the selected immune-related factors except c-LYZ might be in the same responsive regulatory network after challenged with four pathogenic bacteria. Altogether, A. japonicus immune system exhibited high complexity in regulation during organism development and after bacterial challenges. [ABSTRACT FROM AUTHOR]

In order to preliminarily illustrate the functional differences of phenoloxidases (POs) in Apostichopus japonicus , the full-length cDNAs of two POs (named as AjPOⅡ and AjPOⅢ, respectively) were cloned from the coelomocytes of A. japonicus using 3′- and 5′-rapid amplification of cDNA ends method, and combined with the previously acquired full-length cDNA of a laccase-type PO from A. japonicus (Accession No. KF040052 , named as AjPOⅠ), the sequence structure and phylogenic status of POs from A. japonicus (AjPOs) were comparatively analyzed, and the transcriptional expression of AjPOs in different tissues, at different developmental stages and after different bacterial challenges was determined with quantitative real-time PCR method. Sequence analysis indicated AjPOⅡ and AjPOⅢ were both laccase-type POs, coincident to the results of phylogenic analysis. Sequence analysis also showed that AjPOⅠ had a transmembrane domain (J. Jiang et al., 2014), AjPOⅡ contained a signal peptide, and AjPOⅢ possessed a signal peptide and a transmembrane domain, implying that three AjPOs might play different roles in immune and physiological processes. Transcriptional expression analysis showed that AjPOⅡ and AjPOⅢ were most abundant in tube feet, while AjPOⅠhad the highest expression level in coelomocytes (J. Jiang et al., 2014), suggesting that AjPOⅠ may be mainly involved in immune response, while AjPOⅡ and AjPOⅢ are probably responsible for other physiological processes in addition to immune response. Besides, three AjPOs were determined to have different expression patterns during organism development and different spectrums of response against bacteria, which further indicated that there might be immune and physiological functional differentiation among three AjPOs. [ABSTRACT FROM AUTHOR]

In order to understand the effects of seasonal change on the immunity of sea cucumber Apostichopus japonicus cultured in pond, A. japonicus with body weight of 12.2 ± 4.5 g (sample A) and 32.6 ± 7.1 g (sample B), respectively, were collected monthly and randomly from a typical pond during a year cycle and employed for the evaluation of immunocompetence. Simultaneously, the environmental factors in the pond including water temperature, pH, salinity and dissolved oxygen (DO) were measured using a handheld multiparameter meter. The activities of acid phosphatase (ACP), alkaline phosphatase (ALP), lysozyme ( LYZ), phenoloxidase (PO), superoxide dismutase ( SOD), catalase ( CAT) and myeloperoxidase ( MPO) in the coelomic fluid were selected for the evaluation of A. japonicus immunocompetence and determined using biochemical methods. The results showed that in both samples, the activities of all determined enzymes had small values in winter and early spring, and LYZ, CAT and MPO activities also presented small values in summer, suggesting that pond-cultured A. japonicus underwent immunosuppression twice during a year cycle, and the immunosuppression occurred in winter and early spring was more severe than that occurred in summer. In addition, most of the determined enzymes showed different variations between the two samples, and had significantly negative correlation with protein concentration, which was significantly and negatively correlated with water temperature, revealing that body weight and water temperature might have crucial effects on the immunity of A. japonicus cultured in pond. [ABSTRACT FROM AUTHOR]

In order to preliminarily understand the immune difference between females and males in the sea cucumber Apostichopus japonicus , the activities assay of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), phenoloxidase (PO), acid phosphatase (ACP) and alkaline phosphatase (ALP) with biochemical methods, the detection of PO isozymes with native-PAGE and catechol staining, and the test of antibacterial activities with bacterial growth curve determination method were performed in this study using cell-free coelomic fluid (CCF) and coelomocyte lysate supernatant (CLS) from females and males as the samples. The PO activities were not detected in the CLS and showed no significant difference between the CCF from females and males. However, totally five PO isozyme bands were detected in the CLS of females while only four were detected in the CLS of males after zymogram analysis. These results implied that the PO isozymes in the coelomocytes of viripotent A. japonicus were inactive under natural condition and may be activated by some certain treatments during native-PAGE, and PO might play different immune and physiological roles between females and males. In addition, the activities of SOD, CAT, POD and ALP in the CCF and the activities of CAT, POD, ACP and ALP in the CLS from males were all significantly higher than those from females. The results collectively suggested that in viripotent A. japonicus , the gender had a remarkable effect on the immunity, and the immunocompetence of males might have an advantage over that of females. Furthermore, the activities of all determined enzymes except PO and the number of detected PO isozymes showed higher values in CLS than in CCF, implying that in viripotent A. japonicus , the coelomocytes might take more immune responsibility in comparison with CCF. [ABSTRACT FROM AUTHOR]

The immune-related enzymes in marine animals are very sensitive to divalent metal ions. To investigate the roles divalent metal ions play in the influence on the immunity of sea cucumber Apostichopus japonicus, one of the most important commercial species in Asian countries, the effects of eight divalent metal ions at concentrations of 2.5, 5, 10, 15, 20, 25 and 30 mmol L−1 on the activities of superoxide dismutase (SOD), phenoloxidase (PO), acid phosphatase (ACP), alkaline phosphatase (AKP) and myeloperoxidase (MPO) in coelomic fluid were determined with the nitro blue tetrazolium chloride (NBT) method, dopachrome formation method, p-nitrophenyl phosphate ( pNPP) method and 3,3′,5,5′-tetramethyl benzidine (TMB) method. The results indicated that Mg2+ enhanced the activities of SOD, PO, ACP and AKP significantly and showed no obvious effect on MPO activity; Zn2+ increased the activities of SOD, ACP and AKP, and showed no obvious effect on the activities of PO and MPO; Cu2+ enhanced the activities of ACP, AKP and MPO and activated SOD and PO at a certain concentration range; Ca2+ and Mn2+ inhibited the activities of ACP and AKP; Fe2+ had strong inhibitory effect on SOD activity; Pb2+ showed inhibitions on the activities of SOD, PO, ACP and AKP; and Cd2+ inhibited MPO activity greatly. The data obtained in this study collectively suggest that Mg2+, Zn2+ and Cu2+ have potential in promotion of A. japonicus immunity, while Ca2+, Fe2+, Pb2+, Cd2+ and Mn2+ might be limiting factors to the immune response of A. japonicus. [ABSTRACT FROM AUTHOR]

Three proteins with PO-like activities in the coelomocytes of sea urchin Strongylocentrotus nudus were identified using electrophoretic method and named as SnPO1, SnPO2 and SnPO3 according to their molecular mass from high to low. The SnPOs were characterized for substrate specificity and the effects of temperature, pH, divalent metal ions and inhibitors on PO activities. They showed oxidative activities to L-3,4-dihydroxyphenylalanine. ( l -DOPA), dopamine and hydroquinone, but failed to oxidize tyrosine, which illustrated the three proteins had laccase-like PO activities. The optimum temperature for the activities of SnPO1, SnPO2 and SnPO3 was 75 °C, 70 °C, 40 °C, and the optimum pH was 7.0, 9.0, 8.0, respectively. The SnPOs were notably activated after being incubated in boiled water for 60 min, suggesting that the three proteins are thermophilic. The activity of SnPO1 was greatly enhanced by Cu 2+ , Mn 2+ and Fe 2+ and inhibited by Pb 2+ , Cd 2+ , EDTA, DETC, sodium sulfite and ascorbic acid, but SnPO2 and SnPO3 were not obviously affected by Pb 2+ and Cd 2+ , suggesting the three proteins are copper-containing, and the catalytic properties of SnPO1 might be different from those of SnPO2 and SnPO3. Taken together, SnPO1, SnPO2 and SnPO3 might play different roles in the immune and physiological processes of S. nudus . [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs) comprise a group of heterogeneous and immature myeloid-derived cells. MDSCs accumulate in the blood, lymphoid organs, spleens and tumor tissues under different pathogenic conditions such as infection, trauma, hematosepsis, and especially oncogenesis. MDSCs can suppress both adaptive and innate immunities through multiple mechanisms. However, most of our knowledge of MDSCs is based on pre-clinical studies. Clinical observations have shown that the number of MDSCs in the peripheral blood of patients is closely related to tumor stage, tumor burden, remote metastasis and prognosis, though inconsistencies in MDSC phenotypes among cancer patients mean that results have been inconclusive, and subsequent research progress has been slow. This review summarizes recent studies that have investigated MDSCs in cancer patients. [ABSTRACT FROM AUTHOR]

Avian pathogenic E. coli and human extraintestinal pathogenic E. coli serotypes O1, O2 and O18 strains isolated from different hosts are generally located in phylogroup B2 and ST complex 95, and they share similar genetic characteristics and pathogenicity, with no or minimal host specificity. They are popular objects for the study of ExPEC genetic characteristics and pathogenesis in recent years. Here, we investigated the evolution and genetic blueprint of APEC pathotype by performing phylogenetic and comparative genome analysis of avian pathogenic E. coli strain IMT5155 (O2:K1:H5; ST complex 95, ST140) with other E. coli pathotypes. Phylogeny analyses indicated that IMT5155 has closest evolutionary relationship with APEC O1, IHE3034, and UTI89. Comparative genomic analysis showed that IMT5155 and APEC O1 shared significant genetic overlap/similarities with human ExPEC dominant O18:K1 strains (IHE3034 and UTI89). Furthermore, the unique PAI I5155 (GI-12) was identified and found to be conserved in APEC O2 serotype isolates. GI-7 and GI-16 encoding two typical T6SSs in IMT5155 might be useful markers for the identification of ExPEC dominant serotypes (O1, O2, and O18) strains. IMT5155 contained a ColV plasmid p1ColV5155, which defined the APEC pathotype. The distribution analysis of 10 sequenced ExPEC pan-genome virulence factors among 47 sequenced E. coli strains provided meaningful information for B2 APEC/ExPEC-specific virulence factors, including several adhesins, invasins, toxins, iron acquisition systems, and so on. The pathogenicity tests of IMT5155 and other APEC O1:K1 and O2:K1 serotypes strains (isolated in China) through four animal models showed that they were highly virulent for avian colisepticemia and able to cause septicemia and meningitis in neonatal rats, suggesting zoonotic potential of these APEC O1:K1 and O2:K1 isolates. [ABSTRACT FROM AUTHOR]

Abstract: Phenoloxidase (PO) is a crucial immune-related enzyme in invertebrates. In this study, three POs of the sea cucumber Apostichopus japonicus were detected in coelomic fluid using linear-gradient native-PAGE combined with catechol staining and then partially purified by gel excising. The results showed that the three POs had a color of mahogany (AjPO1), yellow (AjPO2) and purple (AjPO3) respectively with molecular weights smaller than 21kDa in native-PAGE after staining with catechol. Enzymatic activities analysis revealed that AjPO1, AjPO2 and AjPO3 had optimal temperature of 45, 95 and 85°C and pH of 5.0, 8.0 and 8.0, respectively. Kinetic analysis showed that the K m values of AjPO1 for catechol, l-DOPA, dopamine and hydroquinone were 3.23, 0.86, 3.98 and 1.20mmol/l, respectively, those of AjPO2 were 0.31, 0.38, 2.05 and 1.30mmol/l, respectively, and those of AjPO3 were 5.95, 1.28, 5.81 and 0.62mmol/l, respectively. These results suggest that the three POs are laccase-type phenoloxidase. The activities of all three A. japonicus POs were significantly promoted by Ca2+, Mg2+ and Mn2+, and strongly inhibited by ethylenediamine tetraacetic acid disodium (EDTA), sodium diethyldithiocarbamate (DETC) and some common antioxidants. The inhibitions by EDTA and DETC suggest that the three A. japonicus POs are copper-containing metalloenzymes. Immune-responsive analysis showed that the total PO activities in coelomocytes (TPAC) increased greatly after lipopolysaccharide (LPS) challenge and declined significantly after polyinosinic–polycytidylic acid (PolyI:C) challenge, implying that A. japonicus PO immune system, which is composed of several isoenzymes with different characteristics, is closely involved in the defense against the infection of Gram-negative bacteria and double-stranded RNA viruses. [Copyright &y& Elsevier]

Abstract: Phenoloxidase (PO) is a crucial component of the immune system of echinoderms. In the present study, the full-length cDNA of PO (AjPO) was cloned from coelomocytes of the sea cucumber Apostichopus japonicus using 3′- and 5′-rapid amplification of cDNA ends (RACE) PCR method, which is 2508 bp, with an open reading frame (ORF) of 2040 bp encoding 679 amino acids. AjPO contains a transmembrane domain, and three Cu-oxidase domains with copper binding centers formed by 10 histidines, one cysteine and one methionine respectively. Phylogenetic analysis revealed that AjPO was clustered with laccase-type POs of invertebrates. Using the isolated membrane proteins as crude AjPO, the enzyme could catalyze the substrates catechol, L-3,4-dihydroxyphenylalanine (l-DOPA), dopamine and hydroquinone, but failed to oxidize tyrosine. The results described above collectively proved that AjPO was a membrane-binding laccase-type PO. The quantitative real-time PCR (qRT-PCR) analysis revealed that AjPO mRNA was expressed in muscle, body wall, coelomocytes, tube feet, respiratory tree and intestine with the highest expression level in coelomocytes. AjPO could be significantly induced by lipopolysaccharide (LPS), peptidoglycan (PGN), Zymosan A and polyinosinic-polycytidylic acid (PolyI:C), suggesting AjPO is closely involved in the defense against the infection of bacteria, fungi and double-stranded RNA viruses. [Copyright &y& Elsevier]

Aim: The aim was to compare the efficacy and toxicity of paclitaxel plus platinum (TP) with gemcitabine plus platinum (GP) in untreated advanced non-small-cell lung cancer by a meta-analysis. Methods: An extensive literature search was performed for relevant randomized controlled trials. Studies were evaluated for eligibility and quality, and then the data were extracted and analyzed using Review Manager 5.1 software. Publication bias was evaluated according to Begg's funnel plot and Egger's test using Stata/SE version 10.1 software. Results: Six randomized controlled trials including 2,793 patients were ultimately identified. The meta-analysis demonstrated that the efficacy was comparable between TP and GP regimens according to the pooled relative risks (RRs) for overall response rate [0.99, 95 % confidence interval (CI) = 0.88-1.13, p = 0.92], disease control rate (0.96, 95 % CI = 0.90-1.03, p = 0.24) and 1-year survival (0.99, 95 % CI = 0.90-1.09, p = 0.87), and the hazard ratios for overall survival (1.06; 95 % CI = 1.00-1.13, p = 0.07) and time-to-progression of disease (1.05, 95 % CI = 0.97-1.14, p = 0.20). Grade 3-4 nausea or vomiting, anemia and thrombocytopenia were less frequent in the TP group (RR = 0.53, 95 % CI = 0.35-0.78, p = 0.002; RR = 0.37, 95 % CI = 0.30-0.45, p < 0.00001; RR = 0.20, 95 % CI = 0.14-0.27, p < 0.00001; respectively). Grade 3-4 sensory neuropathy, fatigue and neutropenia were comparable between the two groups. Sensitivity analyses in studies of paclitaxel compared with gemcitabine combined with the same platinum strengthened the above conclusion. Conclusions: Our meta-analysis showed that paclitaxel plus platinum had similar efficacy and less toxicity compared with gemcitabine plus platinum in first-line treatment of advanced non-small-cell lung cancer. [ABSTRACT FROM AUTHOR]

Peptidoglycan recognition proteins (PGRPs) comprise a family of pattern recognition receptors (PRRs) with an important role in innate immunity. Here, we amplified the full-length cDNA of a novel PGRP from the sea cucumber A. japonicus (named AjPGRP-S1) using RACE. Subsequently, we prepared a codon-optimized recombinant AjPGRP-S1 (rAjPGRP-S1) protein and raised a polyclonal antibody against rAjPGRP-S1 by immunizing rabbits. At the transcriptional level, the tissue expression pattern of AjPGRP-S1 was determined by in situ hybridization and RT-qPCR, while the gene expression of AjPGRP-S1 after microbial polysaccharide challenge was also evaluated by RT-qPCR. Amidase activity was measured using the microplate method; the pathogen recognition characteristics were determined by ELISA and indirect immunofluorescence assay; and the immune factors that interact with AjPGRP-S1 were screened and identified via pull-down assay combined with LC-MS/MS. The AjPGRP-S1 protein was predicted to contain a signal peptide, a PGRP domain, and a molecular mass of 24.6 kDa, but lacked a cysteine residue that is indispensable for the formation of a Zn2+-binding site and amidase activity. Indeed, no amidase activity was detected from rAjPGRP-S1. These results indicated that AjPGRP-S1 might be a secretory, short-type, and recognition-type PGRP. AjPGRP-S1 transcripts were relatively highly abundant in coelomocytes and were markedly induced by challenge with diaminopimelic acid (DAP)-type peptidoglycan (PGN), suggesting that AjPGRP-S1 is mainly expressed by coelomocytes and might play a crucial role in the defense against Gram-negative bacteria. rAjPGRP-S1 was determined to be capable of binding to DAP-type PGN, lysine (Lys)-type PGN, β-1,3-glucan, Vibrio splendidus , Pseudoalteromonas nigrifaciens , Shewanella baltica , Bacillus cereus , Escherichia coli , and Staphylococcus aureus , but not lipopolysaccharide or mannan, implying that AjPGRP-S1 may have a broad-spectrum pathogen recognition ability. Additionally, rAjPGRP-S1 was found to interact either directly or indirectly with multiple soluble and insoluble PRRs and diverse antioxidation-, antistress-, complement system-, bacteria lysis-, and immune response-related factors, as well as several potential immunomodulatory factors, indicating that complete pathogen recognition by the A. japonicus immune system likely requires the synergistic activity of AjPGRP-S1 and other PRRs. These results further implied that AjPGRP-S1 might transduce the immune signal generated following pathogen recognition to multiple immune effectors, thereby inducing both pathogen-attack-oriented and self-protection-oriented immune reactions, as well as to potential immunomodulatory factors so as to adjust the response of the A. japonicus immune system. • AjPGRP-S1 is a secretory and recognition-type PGRP. • AjPGRP-S1 was mainly expressed by coelomocytes. • AjPGRP-S1 showed notable response to DAP-type PGN challenge. • AjPGRP-S1 has broad-spectrum pathogen recognition ability. • AjPGRP-S1 showed direct or indirect interaction with multiple immune factors. [ABSTRACT FROM AUTHOR]

Abstract: Next generation 454 pyrosequencing technology for whole bacterial genome sequencing involves a deep sequencing strategy with at least 15–20× in depth proposed by official protocols but usually done with over 20× in practices. In this study, we carried out a comprehensive evaluation of quality of the de novo assemblies based on realistic pyrosequencing simulated data from 1480 prokaryote genomes and 7 runs of machine-generated data. Our results demonstrated that for most of the prokaryote genomes, 6–10× sequencing in qualified runs with 400bp reads could produce high quality draft assembly (>98% genome coverage, <100 contigs with N50 size >100kb, single base accuracy >99.99, indel error rate <0.01%, false gene loss/duplication rate <0.5%). Our study proves the power of low depth pyrosequencing strategy, which provides a cost-effective way for sequencing whole prokaryote genomes in a short time and enables further studies in microbial population diversity and comparative genomics. [Copyright &y& Elsevier]

Abstract: Phenoloxidase (PO) was purified from hemocytes of the scallop Chlamys farreri using native-PAGE and gel permeation column chromatography, and then substrate specificity and antibacterial activity generated from reaction products of purified PO were analyzed. The results showed purified PO had a molecular mass of 576 kDa in native-PAGE and 53 kDa in denatured PAGE, and could catalyze the substrates L-3,4-dihydroxyphenylalanine (L-DOPA), dopamine, catechol and hydroquinone suggesting it is a type of p-diphenoloxidase. Using dopamine as a substrate, PO reaction products significantly inhibited the growth of Vibrio alginolyticus, Vibrio parahaemolyticus and Aeromonas salmonicida. No significant inhibition was found in Streptococcus dysgalactiae, Streptococcus iniae, Micrococcus lysodeikticus and Edwardsiella tarda. When L-DOPA was used as a substrate, significant inhibition occurred in A. salmonicida only. [Copyright &y& Elsevier]

Purpose. A meta-analysis of randomized controlled trials was performed to compare the efficacy, quality of life (QOL), symptom improvement and toxicities of gefitinib with docetaxel in previously treated advanced non-small-cell lung cancer. Methods. The PubMed database, the Cochrane Library and references of published trials were searched. Two reviewers independently assessed the quality of the trials and extracted data. The hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), relative risks (RRs) for overall response rate, QOL and symptom improvement, and odds ratios (ORs) for main toxicities were pooled using STATA package. Results. Four multicenter, randomized controlled trials involving 2257 patients with previously treated advanced NSCLC were ultimately analyzed. The pooled HRs showed no significant difference in OS and PFS between the two groups (HR == 1.02, 95% CI == 0.92--1.12, p == 0.70; HR == 0.97, 95% CI == 0.88--1.07, p == 0.57, respectively). Gefitinib significantly improved overall response rate (RR == 1.58, 95% CI == 1.02--2.45, p == 0.04) and QOL (RR == 1.55, 95% CI == 1.27--1.88, p == 0.00 by Functional Assessment of Cancer Therapy-Lung and RR == 1.86, 95% CI == 1.43--2.42, p == 0.00 by Trial Outcome Index, respectively). Gefitinib had fewer grade 3 or 4 neutropenia and fatigue (OR == 0.02, 95% CI == 0.01--0.03, p == 0.00; and OR == 0.47, 95% CI == 0.32--0.70, p == 0.00, respectively), but more grade 3 or 4 rash (OR == 2.87, 95% CI == 1.24--6.63, p == 0.01) than docetaxel. The grade 3 or 4 nausea, vomiting and diarrhea and symptom improvement were comparable between the two drugs. Conclusions. In conclusion, although similar OS and PFS, gefitinib showed an advantage over docetaxel in terms of objective response rate, QOL and tolerability. Therefore, gefitinib is an important and valid treatment option for previously treated advanced non-small-cell lung cancer patients. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To compare the efficacy and toxicities of chemotherapy plus cetuximab (Erbitux, E; E-chemo) with chemotherapy alone (chemo alone) in patients with previously untreated advanced non-small-cell lung cancer (NSCLC). The primary endpoint was overall survival; the secondary endpoints were progression-free survival, overall response rate, one-year survival and safety. Methods: The PubMed database, the Cochrane Library, conference proceedings, database of ongoing trials and references of published trials and reviews were screened. Two reviewers independently assessed the quality of the trials and extracted data. The hazard ratios (HRs) for overall survival and progression-free survival, relative risks (RRs) for overall response rate and one-year survival, and odds ratios (ORs) for the different types of toxicity were pooled using STATA SE10.1 package. Results: Four trials involving 2018 patients with previously untreated NSCLC were ultimately analyzed. The pooled HR for overall survival (HR, 0.87; 95%CI, 0.79–0.96; p =0.004) was in favor of E-chemo, which also gave rise to a higher overall response rate (RR, 1.19; 95%CI, 1.04–1.37; p =0.013). The analysis failed to show benefit of E-chemo in progression-free survival (HR, 0.91; 95%CI, 0.83–1.00; p =0.06) and one-year survival (RR, 1.10; 95%CI, 0.98–1.26; p =0.172). E-chemo indeed caused more grade 3/4 rash and infusion reaction (OR, 43.86; 95%CI, 12.46–154.44; p =0.000; OR, 3.69; 95%CI, 1.89–7.25; p =0.000; respectively). Conclusion: Our data showed that the addition of cetuximab to chemotherapy would improve overall survival and overall response rate. It may provide new option for clinical treatment for untreated advanced non-small-cell lung cancer. The side effects of E-chemo are predictable and manageable. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Whether platinum plus gemcitabine or vinorelbine are equally effective in the treatment of advanced non-small-cell lung cancer (NSCLC) is still controversial, a meta-analysis was performed to compare the gemcitabine plus platinum with vinorelbine plus platinum regimens in first-line treatment of advanced NSCLC. Methods: A literature search was performed in PubMed database, the Cochrane Central Register of Controlled Trials (CENTRAL) database, the Physician Data Query (PDQ) database, EMBASE and the American Society of Clinical Oncology (ASCO) annual meeting abstracts. The following keywords were used: “non small cell lung cancer,” or “Carcinoma, Non-Small-Cell Lung”. Reference lists of original articles and review articles were also examined. The published languages and years were not limited. The trials searched were evaluated for eligibility and quality, and then the data were abstracted and analyzed. Endpoints were overall survival, overall response, and toxicity. Statistical tests for heterogeneity were one-sided; statistical tests for effect estimates were two-sided. Results: Nine randomized controlled trials involving 2186 patients were identified from 453 reports. They were all published as full-text articles. The intention-to-treatment (ITT) analysis demonstrated that the patients with gemcitabine plus platinum regimens had an equal overall response rate in comparison with vinorelbine plus platinum regimens (RR, 0.91; 95%CI, 0.81–1.03; P =0.15). Furthermore, the 1-year survival rate for the two platinum-based regimens were comparable (RR, 1.06; 95%CI, 0.96–1.18; P =0.27). Subgroup analysis comparing the cisplatin plus gemcitabine or vinorelbine had achieved the same results. Vinorelbine plus platinum regimens led to more frequent grade 3 or 4 of neutropenia, nephrotoxicity, constipation and phlebitis (OR, 0.37; 95%CI, 0.26–0.52; P <0.00001; OR, 0.38; 95%CI, 0.25–0.57; P <0.00001; OR, 0.50; 95%CI, 0.27–0.92; P =0.03 and OR, 0.13; 95%CI, 0.05–0.32; P <0.00001, respectively), while gemcitabine plus platinum chemotherapy inclined to developing more grade 3 or 4 thrombocytopenia (OR, 11.37; 95%CI, 4.56–28.38; P <0.00001). The incidence of grade 3 or 4 anemia, nausea and vomiting were almost comparable between the two arms (OR, 1.12; 95%CI, 0.62–2.02; P =0.71 and OR, 0.72; 95%CI, 0.41–1.28; P =0.27, respectively). Similar results were also achieved in subgroup analyses between the gemcitabine and vinorelbine in combination with the cisplatin. Conclusion: It could be concluded that the efficacy were similar between the platinum plus gemcitabine or vinorelbine regimens. The choice of platinum plus gemcitabine or vinorelbine depends on the toxicity of the drugs and patients’ tolerance. [Copyright &y& Elsevier]

Summary: Objective: Since the debate still exists whether cisplatin-based and carboplatin-based chemotherapy are equally effective for advanced non-small-cell lung cancer (NSCLC), a meta-analysis of trials was performed to compare the cisplatin-based with carboplatin-based regimens in first line chemotherapy of advanced NSCLC. Methods: A literature search was performed in PubMed database, the Cochrane Central Register of Controlled Trials (CENTRAL) database, the Physician Data Query (PDQ) database and the American Society of Clinical Oncology (ASCO) annual meeting abstracts in January 2007. The following keywords were used: “non small cell lung cancer,” or “Carcinoma, Non-Small-Cell Lung”. Reference lists of original articles and review articles were also examined. The published languages and years were not limited. The trials searched were evaluated for eligibility and quality, and then the data were abstracted and analyzed. Results: Eighteen randomized controlled trials (6906 patients) were identified from 4240 reports. The intention to treatment (ITT) analysis demonstrated that the cisplatin-based regimens had a higher overall response rate in comparison with carboplatin-based regimens (RR, 0.91; 95%CI, 0.84–0.99; P =0.02). However, the 1-year survival rate for the two platinum-based regimens were comparable (RR, 1.00, 95%CI, 0.94–1.07; P =0.93), Both subgroup analysis comparing the doublet or triplet regimens of cisplatin or carboplatin in combination with new agents and the same agents had achieved the same results. Cisplatin-based chemotherapy led to more frequent grade 3 or 4 of nausea and vomiting, and nephrotoxicity (OR, 0.39; 95%CI, 0.30–0.52; P <0.00001 and OR, 0.31; 95%CI, 0.17–0.56; P =0.0001), while carboplatin-based chemotherapy inclined to developing more grade 3 or 4 thrombocytopenia, however, there were no statistical significance (OR, 1.63; 95%CI, 0.94–2.82; P =0.08). The risk of grade 3 or 4 anemia, neutropenia and neurotoxicity was almost comparable between the two arms (OR, 0.78; 95%CI, 0.59–1.02; P =0.07; OR, 1.08; 95%CI, 0.80–1.45; P =0.61 and OR, 1.59; 95%CI, 0.81–3.14; P =0.18, respectively). The subgroup analyses of the comparison between the doublet or triplet regimens of cisplatin and carboplatin in combination with the same agents, respectively, also achieved similar results, with the exception of thrombocytopenia between the two groups (OR, 1.94; 95%CI, 1.47–2.68; P <0.00001), which showed statistically significant. Cisplatin arm inclined to causing more treatment-related deaths compared as carboplatin arm, but there was no statistical significance (OR, 0.70; 95%CI, 0.48–1.02; P =0.06). Conclusion: Given cisplatin-based regimens had a higher overall response rate as compared with carboplatin-based regimens, there was not a survival advantage in the cisplatin group. Therefore, the toxicity profile might play an important role in decision to choose cisplatin-based or carboplatin-based regimens. [Copyright &y& Elsevier]

Background: Alzheimer’s disease associated βAPP is sequentially endoproteolyzed by α/β-secretase and γ-cleavage. In the process, extracellular shedding by α-secretase (ADAM 9/10/17) or β-secretase (BACE 1/2) at position L17 or D1 (Aβ numbering) are prerequisites for the generation of P3 or Aβ, respectively. In addition, several alternative extracellular cleavage sites in βAPP have been reported at position I−6, V−3, R5, E11, F20, and A21. Among these sites, position R5 is considered to be cleaved by α-secretase-like activity, whereas position E11, F20 and A21 are cleaved by β-secretase. Therefore, extracellular shedding of βAPP is thought to be mediated exclusively by α/β-secretase activities. However, so far the characteristics of cleavages at position V−3 and I−6 are not well understood. The aim of this study is to characterize these two cleavages of βAPP. Methods: We analyzed the conditioned media of βAPP wt or sw expressing cells with or without pharmacological agents. Results: Here, we show that the cleavage at position I−6 of βAPP has characteristics distinct from that of α/β-secretase, while the cleavage at V−3 seems to be mediated by β-secretase. Although inhibition of endocytosis enhances the cleavages at both V−3 and I−6, PMA, an α-secretase stimulator, treatment enhances neither of these cleavages. Interestingly, a β-secretase inhibitor, z-VLL-CHO, suppressed V−3 but not I−6 cleavage. The pathological βAPP Swedish mutant adjacent to the cleavage sites shows similar effects. Conclusions: Our data demonstrate that neither α nor β-secretase undergoes extracellular shedding at I−6 of βAPP. Therefore, our data may indicate a novel alternative βAPP degradation pathway which is up-regulated upon low level of endocytosis. [ABSTRACT FROM AUTHOR]

R2862 --> The ventromedial nucleus of the hypothalamus (VMH) was the first site to be recognized as a key player in body weight regulation. The VMH has also been implicated in brown adipose tissue (BAT) thermoregulation, sympathetic nerve activity and glucose homeostasis. Within the VMH, steroidogenic factor 1 (SF1) neurons expressing receptors that binds various hormonal signals have emerged as critical mediators of metabolic control. In this study, we assessed how Designer Receptors Exclusively Activated by Designer Drugs (DREADD)‐mediated activation of SF1 neurons affect food intake, glucose homeostasis, insulin sensitivity and sympathetic nerve activity. Using SF1Cre+ male mice, we found that DREADD‐mediated activation of SF1 neurons caused a dramatic feeding stimulatory response within 4h of CNO injection (0.75±0.16g relative to 0.13±0.07g in control SF1Cre‐ mice, P<0.05). Interestingly, in male mice SF1 neuron‐specific activation induces BAT sympathetic nerve activation without affecting renal sympathetic tone. In female mice, food intake and BAT sympathetic traffic were not altered after activation of SF1 neurons. On the other hand, insulin sensitivity was significantly attenuated only in females following SF1 neuron activation (100.20±13.07mmol/L vs 25.25±12.15mmol/L in control at 2h, P<0.05). Glucose homeostasis was not affected upon SF1 neuron activation in both male and female mice. Notably, activation of SF1 neurons increased blood pressure and heart rate in mice fed high fat/high sucrose diet. These results show that VMH SF1 neurons regulate food intake, sympathetic tone and insulin sensitivity in a sex‐specific manner and that SF1 neurons contribute to regulation of cardiovascular function. Our findings provide new insight into a previously unappreciated role of VMH SF1 neuron in the control of regional sympathetic nerve traffic and cardiovascular function. [ABSTRACT FROM AUTHOR]

Bacteria communities in the aquaculture environment have been shown to greatly influence the growth of culture species. The sea cucumber (Apostichopus japonicus) is one of the most important aquaculture species in China, with numerous economic benefits. The growth and physiological characteristics of A. japonicus exhibit remarkable seasonal variation. However, current knowledge regarding the bacterial communities in A. japonicus culture ponds and their potential roles in the regulation of A. japonicus growth and physiology remain unclear. In the present study, Illumina sequencing based on the bacterial 16S rRNA gene was used to investigate the variations in bacterial communities in the surface water and sediment of A. japonicus culture ponds for a period of 1 year. The sediments exhibited a higher diversity of bacterial communities, and a higher abundance of microorganisms involved in sulfur metabolism; however, the surface water had a higher abundance of bacterial species associated with the degradation of organic matter. Furthermore, the bacterial communities in the water column showed a "3 + 1" monthly pattern and those in the sediments exhibited a seasonal succession. The higher abundances of bacteria associated with organic pollution degradation and functions associated with bio-active compound secretion were detected in water samples collected in April, August, and December. In contrast, bacteria that are considered to be food sources for A. japonicus were more abundant in pond sediments in autumn and spring. Finally, correlation analysis demonstrated that water temperature negatively regulated the sulfur cycling efficiency of bacterial communities in sediments of A. japonicus culture ponds. This study provides an important theoretical basis for the micro-ecological regulation of pond-cultured A. japonicus. Unlabelled Image • Microbiomes in the water and sediment of sea cucumber culture pond were compared. • Pond sediments had a higher abundance of bacteria involved in sulfur metabolism. • Water bacteria could remove more organic pollutants in April, August, and December. • Pond water bacteria could be more responsible to the degradation of organic matters. • Temperature negatively regulated the sulfur cycling of bacteria in pond sediments. [ABSTRACT FROM AUTHOR]

Due to the importance of characteristics associated with the immunity and physiology of organisms, gender is always taken into account when improving the breeding efficiency of economically important animals. Protein variations in the cell-free ceolomic fluid (CCF) of male and female Apostichopus japonicus before and after spawning were investigated using a comparative proteomic approach, for the purpose of understanding the influence of gender and gender associated reproductive processes on humoral immunity and physiological characteristics of the sea cucumber, A. japonicus. A total of 6839 peptides were obtained and a set of 1466 proteins were identified in the CCF of male and female A. japonicus before and after spawning. Partial least squares discrimination analysis indicated that protein expression profiles in the CCF of A. japonicus were significantly affected by both gender and reproductive processes. In addition, the differentially expressed proteins (DEPs) in the CCF of different genders and reproductive stages of A. japonicus were determined and immune-related proteins in these DEPs were screened. Findings revealed that the alternative pathway of complement activation in both male and female A. japonicus before spawning might take precedence over that after spawning. Further KEGG enrichment analyses of DEPs suggested that the capacity of muscle contraction in A. japonicus females, and food digestion, nutrition absorption, epithelial differentiation as well as growth in A. japonicus males might be enhanced after spawning. Further, compared with A. japonicus females, males may have an advantage in growth in the stages following spawning. Besides, according to KEGG annotation related to metabolism, arginine biosynthesis and purine metabolism were dominant in the CCF of male and female A. japonicus , respectively, suggesting notable metabolic differences in female and male A. japonicus. Overall, our study provides new insight into the understanding of molecular mechanisms underlying gender-determined immune and physiological differences in A. japonicus. The current study aimed to reveal the gender differences in humoral immunity and physiological characteristics associated with reproduction in the sea cucumber Apostichopus japonicus. To the best of our knowledge, this is the first proteomic study analyzing the differences in protein profile between male and female A. japonicus. By analyzing the expression differences of the proteome via label-free proteomic technology, we revealed that both gender and reproduction could alter the protein composition and abundance in the cell-free colemic fluid (CCF) of A. japonicus. Based on the recognition of differentially expressed proteins (DEPs) related to immune function among the CCFs, shifts in humoral immunity of male and female A. japonicus that underwent reproduction were obtained. Moreover, according to the enrichment analyses of DEPs based on Kyoto Encyclopedia of Genes and Genomes, a draft view of how the male and female A. japonicus affected by reproduction physiologically was drawn. The results suggested that the alternative pathway of complement activation in both male and female A. japonicus were weakened after spawning. In addition, after reproduction, the capacity of muscle contraction might be enhanced in female A. japonicus , and the nutrients consumption, epithelial differentiation and growth might be strengthened in males. Further, ipath analysis indicated that A. japonicus with different genders also had notable differences in metabolism that related to arginine biosynthesis and purine metabolism. The findings presented here will improve the cognition of researchers in the molecular mechanism underlying the gender-determined immune and phyisological differences of A. japonicus and contribute for the meticulous breeding of A. japonicus. Unlabelled Image • Both gender and reproduction affected Apostichopus japonicus immunity and physiology. • A. japonicus alternative complement pathway was depressed after spawning. • The muscle contraction capacity in females might be enhanced after spawning. • The nutrients consumption and growth might be boosted in males after spawning. • The males might have advantage over females in growth after sapwning. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is cancer with the highest morbidity and mortality in the world and poses a serious threat to human health. Therefore, discovering new treatments is urgently needed to improve lung cancer prognosis. Small molecule inhibitors targeting the ubiquitin-proteasome system have achieved great success, in which deubiquitinase inhibitors have broad clinical applications. The deubiquitylase OTUD3 was reported to promote lung tumorigenesis by stabilizing oncoprotein GRP78, implying that inhibition of OTUD3 may be a therapeutic strategy for lung cancer. Results: In this study, we identified a small molecule inhibitor of OTUD3, Rolapitant, by computer-aided virtual screening and biological experimental verification from FDA-approved drugs library. Rolapitant inhibited the proliferation of lung cancer cells by inhibiting deubiquitinating activity of OTUD3. Quantitative proteomic profiling indicated that Rolapitant significantly upregulated the expression of death receptor 5 (DR5). Rolapitant also promoted lung cancer cell apoptosis through upregulating cell surface expression of DR5 and enhanced TRAIL-induced apoptosis. Mechanistically, Rolapitant directly targeted the OTUD3-GRP78 axis to trigger endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP)-DR5 signaling, sensitizing lung cancer cells to TRAIL-induced apoptosis. In the vivo assays, Rolapitant suppressed the growth of lung cancer xenografts in immunocompromised mice at suitable dosages without apparent toxicity. Conclusion: In summary, the present study identifies Rolapitant as a novel inhibitor of deubiquitinase OTUD3 and establishes that the OTUD3-GRP78 axis is a potential therapeutic target for lung cancer. [ABSTRACT FROM AUTHOR]

Background and Purpose: The protein V‐domain immunoglobulin suppressor of T‐cell activation (VISTA) is a novel immune‐checkpoint molecule that belongs to the B7 family and regulates a broad spectrum of immune responses. So far, low MW compounds targeting VISTA for the treatment of autoimmune diseases or inflammation, have not been identified. Experimental Approach We developed a homology modelling for VISTA 3D structure and subsequent virtual screening for low MW ligands binding to VISTA. Visualization of the binding postures of docked ligands with protein VISTA indicated that compound M351‐0056 targeted VISTA. The biological activities of compound M351‐0056 targeting VISTA were investigated in vitro using monocytes and T cells and in vivo, using mice with imiquimod‐induced dermatitis. Key Results: The KD value of M351‐0056 for human VISTA‐extracellular domain was 12.60 ± 3.84 μM as assessed by microscale thermophoresis. M351‐0056 decreased cytokine secretion from PBMCs or human CD4+ T cells, suppressed proliferation of PBMCs and enhanced expression of Foxp3+ T cells. These effects of M351‐0056 modulating VISTA involved the JAK2–STAT2 pathway. Daily administration of M351‐0056 ameliorated imiquimod‐induced psoriasis‐like dermatitis. Expression of mRNA and protein of inflammatory cytokines in psoriatic lesions was decreased after M351‐0056 treatment. Conclusion and Implications: The compound M351‐0056 showed high affinity for VISTA and may modulate its immune function in vitro and in vivo. Our finding provides a lead compound for therapeutically enhancing VISTA‐mediated pathways to benefit the treatment of autoimmune diseases or inflammation. [ABSTRACT FROM AUTHOR]

• miR-318 directly targets the 3′-UTR of AjDNMT1, and downregulates the expression level of AjDNMT1. • miR-318 mimics decreased the expression of AjDNMT1, AjMBP, and AjDMAP, while miR-318 inhibitor increased their expression. • Regulations between miR-318 and AjDNMT1, AjMBP, AjDMAP provide insights into the prevention of A. japonicus SUS. [ABSTRACT FROM AUTHOR]

The design and fabrication of robust metallic states in graphene nanoribbons (GNRs) are challenging because lateral quantum confinement and many-electron interactions induce electronic band gaps when graphene is patterned at nanometer length scales. Recent developments in bottom-up synthesis have enabled the design and characterization of atomically precise GNRs, but strategies for realizing GNR metallicity have been elusive. Here we demonstrate a general technique for inducing metallicity in GNRs by inserting a symmetric superlattice of zero-energy modes into otherwise semiconducting GNRs. We verify the resulting metallicity using scanning tunneling spectroscopy as well as first-principles density-functional theory and tight-binding calculations. Our results reveal that the metallic bandwidth in GNRs can be tuned over a wide range by controlling the overlap of zero-mode wave functions through intentional sublattice symmetry breaking. [ABSTRACT FROM AUTHOR]

In terms to investigate the effect of low-intensity pulsed ultrasound (LIPUS) for differentiation of bone marrow mesenchymal stem cells (BMSCs) and the feasibility of simultaneously inducing into osteoblasts and vascular endothelial cells within the cell culture medium in which two inductive agents are added at the same time with or without LIPUS. Cells were divided into a non-induced group, an osteoblast-induced group, a vascular endothelial-induced group, and a bidirectional differentiation-induced group. Each group was further subdivided into LIPUS and non-LIPUS groups. The cell proliferation in each group was measured by MTT assay. Cell morphological and ultrastructural changes were observed by inverted phase contrast microscopy and transmission electron microscopy. The differentiation of BMSCs was detected by confocal microscopy, flow cytometry and quantitative RT-PCR. Results demonstrated that both osteoblast and vascular endothelial cell differentiation markers were expressed in the bidirectional differentiation induction group and early osteogenesis and angiogenesis appeared. The cell proliferation, differentiation rate and expression of osteocalcin and vWF in the LIPUS groups were all significantly higher than those in the corresponding non-LIPUS group (p <.05), suggesting LIPUS treatment can promote the differentiation efficiency and rate of BMSCs, especially in the bidirectional differentiation induction group. This study suggests the combination of LIPUS and dual-inducing agents could induce and accelerate simultaneous differentiation of BMSCs to osteoblasts and vascular endothelial cells. These findings indicate the method could be applied to research on generating vascularized bone tissue with a shape and function that mimics natural bone to accelerate early osteogenesis and angiogenesis. [ABSTRACT FROM AUTHOR]

Background Transplantation and immunosuppressive therapies are the available treatments for aplastic anemia; however, each strategy has its advantages and disadvantages. Objective The aim of this study was to find a new strategy for aplastic anemia treatment. Design This was an experimental and comparative study. Methods The aplastic anemia model was established by injecting rabbits with benzene and cyclophosphamide. The rabbits with aplastic anemia were divided into low-intensity pulsed ultrasound (LIPUS) and control groups. The distal femoral metaphysis of rabbits in the LIPUS group was treated with ultrasound for 30 days (20 min/d), whereas the control group received a sham treatment. Diarrhea, mortality, and blood cell count were evaluated. The levels of forkhead box P3, interleukin 17, interleukin 4, and interferon gamma were measured using an enzyme-linked immunosorbent assay. Bone marrow hyperplasia was observed by hematoxylin-eosin staining and scanning electron microscopy. Results The numbers of red blood cells (RBCs), white blood cells (WBCs), and platelets (PLTs) were lower, the amount of hematopoietic tissue was lower, and the amount of adipose tissue was higher in the rabbit aplastic anemia model than in the normal rabbits. The numbers of RBCs, WBCs, and PLTs increased after LIPUS treatment. The interleukin 17 level decreased, whereas the forkhead box P3 level increased. The amount of hematopoietic tissue increased, whereas the amount of adipose tissue decreased. Limitations The number of hematopoietic stem cells could not be evaluated. Conclusions LIPUS improved the hematopoietic microenvironment, accelerated the reconstruction of bone marrow cells, and increased the quantity and quality of RBCs, WBCs, and PLTs in the peripheral blood. Hence, it can serve as a novel treatment strategy for aplastic anemia in the future. [ABSTRACT FROM AUTHOR]

Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) has been demonstrated to serve a vital role in tumor progression. However, the biological role and molecular mechanisms of TBL1XR1 in lung squamous cell carcinoma (SCC) remain largely unknown. The purpose of the present study was to investigate the biological role of TBL1XR1 and its mechanism in lung SCC. TBL1XR1 was expressed in a human bronchial epithelial cell line and in lung SCC cell lines. The present study analyzed TBL1XR1-induced proliferation, invasion and migration abilities in vitro using the cell counting kit-8 assay, cell invasion assay and wound healing assay, respectively. This study examined the effects of TBL1XR1 on epithelial-mesenchymal transition (EMT) in lung SCC cells and activation of the transforming growth factor (TGF)-β/mothers against decapentaplegic homolog (Smad) signaling pathway by western blotting. The results indicated that TBL1XR1 was upregulated in lung SCC cells. Overexpression of TBL1XR1 increased the rate of cell proliferation compared with the control group. In vitro, overexpression of TBL1XR1 promoted cell invasion and migration ability compared with the control group. In addition, overexpression of TBL1XR1 produced a mesenchymal phenotype, while cells with downregulated TBL1XR1 produced an epithelial phenotype. Overexpression of TBL1XR1 significantly increased E-cadherin protein expression whilst snail family transcriptional repressor 1 (SNAI1), zinc finger E-box binding homebox 1 (ZEB1), p-Smad2/3, Smad2 and Smad3 protein expression was significantly reduced, compared with the control group. Downregulation of TBL1XR1 produced the opposite results. The present study indicated that TBL1XR1 contributed to lung SCC development and progression, and therefore TBL1XR1 may be a potential therapeutic target. TBL1XR1 may induce EMT of lung SCC cells through activation of the TGF-β/Smad signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract 8-methoxypsoralen (8-MOP) with ultraviolet A radiation therapy (PUVA) is the standard therapy for patients with psoriasis, despite the reported potential risks of 8-MOP-induced cholestatic liver injury in both humans and animals. Usually, patients with chronic cholestasis exhibit lower serum 25-hydroxy vitamin D (25(OH)D) levels. But those patients receiving PUVA for psoriasis showed an increase in serum 25(OH)D levels, probably highlighting that the vitamin D–vitamin D nuclear receptor (VD-VDR) axis play a protective role in 8-MOP-induced hepatotoxicity. The present study confirmed 8-MOP could increase serum 25(OH)D levels in conventional lighting and diet (CLD) and vitamin D deficient (VDD) Sprague-Dawley rats. Potential liver risks were also found in CLD and VDD rats after 8-MOP treatment. We proved that 8-MOP could be a potent ligand for VDR using molecular docking and luciferase report assay. Effect of 8-MOP on VDR subcellular distribution was determined using human liver cell line L02. We found 8-MOP could increase VDR protein expression in the nuclear and cytosol extracts and also total cell extracts in L02. siRNAs for VDR were used to determine the role of VDR in protecting 8-MOP-induced cholestasis and potential cellular mechanisms. The results showed 8-MOP could affect the CYP7A1, SHP and MRP3 expression via VDR, and such effects could be reversed by knockdown of VDR expression, suggesting a vital role of VDR involved in 8-MOP-regulated bile acid synthesis and transportation. In conclusion, these results revealed activation of VD–VDR axis may play a beneficial role in 8-MOP-mediated regulation of bile acid synthesis and transportation. Highlights • Potential liver risks of 8-MOP were found in normal and VDD rats. • Increased serum levels of 25(OH)D were observed in normal and VDD rats. 8-MOP could be a potent ligand for VDR. • VDR is responsible for 8-MOP-regulated expression of CYP7A1, SHP and MRP3. [ABSTRACT FROM AUTHOR]

Bacteria are the most abundant organisms in natural environment and dominant drivers of multiple geochemical functions. Drawing a global picture of microbial community structure and understanding their ecological status remain a grand challenge. As a typical artificial process, aquaculture provides a large amount of foods and creates great economic benefits for human beings. However, few studies are aimed at the microbial community in the aquaculture environment of aquatic plants. We analyzed microbial communities from 21 water samples in a coastal aquaculture area during the whole cultural process of Undaria pinnatifida by using high-throughout sequencing of 16S rRNA gene. The progression of U. pinnatifida aquaculture can be divided into three stages, named Seeding, Growth, and Maturity, respectively. Microbial community structures in water of the aquaculture area were significantly changed during the progression of U. pinnatifida aquaculture. The relative abundance of Flavobacteriia and Thaumarchaeota classes increased in Growth stage, and β-proteobacteria and Acidimirobiia classes decreased with the growth of U. pinnatifida . Meanwhile, environmental factors shaping the microbial community structures were uncovered during the U. pinnatifida aquaculture by using canonical correspondence analysis and Mantel test, in which temperature, dissolved oxygen, pH and nitrogen could be the major influencing factors. In addition, the microbial functions based on KEGG pathways were predicted from the microbial community compositions by PICRUSt. The comparison of predicted functions suggested that Environmental Information Processing and Genetic Information Processing were the functional categories with the most obvious shift in abundance among different stages of U. pinnatifida aquaculture. The findings of this study allowed us to better understand the microbial community in coastal aquaculture systems and the impact of seaweed cultivation on coastal ecosystems. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate the effects of Bacillus licheniformis and combined herbs extracts on the physiological and immune characteristics, intestinal microbiota, and vibriosis resistance of sea cucumber Apostichopus japonicus. The sea cucumbers were fed with basal diets supplemented with B. licheniformis (B group), combined herbs extracts (C group), or both (BC group). The BC group exhibited the better growth performance and higher digestive and immune enzyme activities, whereas the lowest parameters appeared in the control group. This revealed that dietary B. licheniformis and combined herbs extracts in combination could improve digestion, food intake, phosphatase-responsiveness, and oxidation resistance more efficiently compared with the other groups. The BC group was also more capable of regulating intestinal flora balance of sea cucumbers by increasing the beneficial bacteria related to energy synthesis and metabolic conversion, and inhibiting the potential pathogens associated with organic damage and metabolic disorders. Furthermore, the BC group showed greater ability of improving disease resistance by reducing the cumulative mortality rates and the counts of Vibrio splendidus. These results collectively demonstrated that dietary B. licheniformis and combined herbs extracts could improve the physiological and immune parameters, optimize the microbial community, and enhance the resistance to vibriosis of sea cucumbers, and the health-promoting effects were more obvious by supplying them in combination. [ABSTRACT FROM AUTHOR]