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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]

[Display omitted] • The three novel quinoxaline-based PAEs have been successfully prepared. • PAE films exhibit ultra-low D k (2.45–2.87) and D f (0.0019–0.0057) at high frequency. • PAEs show excellent hydrophobic, solubility and thermal properties. With the rapid growth of 5G communication technology, low-dielectric materials can decrease the loss of the signal during transmission. Hence, there is an urgent need to develop high-performance materials with low dielectric constant (D k) and dielectric loss (D f) at high frequency. In this study, we propose a strategy that combines bulk rigid quinoxaline structure and low polarizability trifluoromethyl group to prepare poly (aryl ether)s (PAEs) with low D k and D f at high frequencies. The effect of methyl substituents on the properties of PAEs was focuses on investigated. Accordingly, three difluoro-monomers containing quinoxaline structures were designed and prepared and novel quinoxaline-based PAEs with different numbers of methyl substituents were synthesized by nucleophilic condensation reactions with the bisphenol monomer hexafluorobisphenol A (BP6F). Test results that the resultant PAEs exhibited excellent thermal and solubility properties, with 5 % thermal decomposition temperatures (T d5%) in the range of 500−515 °C and glass transition temperatures (T g) reaching 225 °C. Furthermore, these PAE films show outstanding optical transparency, with cut-off wavelengths of 398−400 nm and above 87 % transmission at 800 nm. Most importantly, the novel PAE films possess ultra-low D k and D f , with the lowest values reaching 2.45 and 0.0024 at 10 GHz and maintain low water absorption (0.53–0.63 %). The excellent properties of novel quinoxaline-based PAEs provide its application potential in the field of high-frequency communications. [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]

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]

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]

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: 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]

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]

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]

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]

Aquaculture pond sediments have a notable influence on the ecosystem balance and farmed animal health. In this study, microalgal-bacterial immobilization (MBI) was designed to improve aquaculture pond sediments via synergistic interactions. The physicochemical characteristics, bacterial communities, and the removal efficiencies of emerging pollutants were systematically investigated. The consortium containing diatom Navicula seminulum and Alcaligenes faecalis was cultivated and established in the free and immobilized forms for evaluating the treatment performance. The results indicated that the immobilized group exhibited superior performance in controlling nutrient pollutants, shaping and optimizing the bacterial community compositions with the enrichment of functional bacteria. Additionally, it showed a stronger positive correlation between the bacterial community shifts and nutrient pollutants removal compared to free cells. Furthermore, the immobilized system maintained the higher removal performance of emerging pollutants (heavy metals, antibiotics, and pathogenic Vibrios) than free group. These findings confirmed that the employment of immobilized N. seminulum and A. faecalis produced more synergistic benefits and exerted more improvements than free cells in ameliorating aquaculture pond sediments, suggesting the potential for engineering application of functional microalgal-bacterial consortium in aquaculture. [Display omitted] • The cooperative interactions of MBI for reducing nutrient pollutants were explored. • MBI performed better in improving physicochemical properties than free system. • The bacterial communities were shaped and optimized by MBI more significantly. • MBI exhibited a higher emerging pollutants removal performance than free system. [ABSTRACT FROM AUTHOR]

S. marcescens FS14 was isolated from an Atractylodes macrocephala Koidz plant that was infected by Fusarium oxysporum and showed symptoms of root rot. With the completion of the genome sequence of FS14, the first comprehensive comparative-genomic analysis of the Serratia genus was performed. Pan-genome and COG analyses showed that the majority of the conserved core genes are involved in basic cellular functions, while genomic factors such as prophages contribute considerably to genome diversity. Additionally, a Type I restriction-modification system, a Type III secretion system and tellurium resistance genes are found in only some Serratia species. Comparative analysis further identified that S. marcescens FS14 possesses multiple mechanisms for antagonism against other microorganisms, including the production of prodigiosin, bacteriocins, and multi-antibiotic resistant determinants as well as chitinases. The presence of two evolutionarily distinct Type VI secretion systems (T6SSs) in FS14 may provide further competitive advantages for FS14 against other microbes. To our knowledge, this is the first report of comparative analysis on T6SSs in the genus, which identifies four types of T6SSs in Serratia spp.. Competition bioassays of FS14 against the vital plant pathogenic bacterium Ralstonia solanacearum and fungi Fusarium oxysporum and Sclerotinia sclerotiorum were performed to support our genomic analyses, in which FS14 demonstrated high antagonistic activities against both bacterial and fungal phytopathogens. [ABSTRACT FROM AUTHOR]

Haemophilus parasuis is the etiological agent of Glässer's disease in pigs and 15 standard serovars were identified. The widespread disease causes great economic loss in the swine industry worldwide. Aiming to investigate the differences in genome composition and functions among various strains, a highly virulent strain ZJ0906 of H. parasuis serovar 12 from China was analyzed and compared with serovar 5 SH0165. Strain ZJ0906 genome is 2,324,740 base pairs with 40.06% genomic GC content. It contains 2,484 open reading frames (ORF) predicted by Glimmer 3.02, of which 2,352 (∼94.7%) were annotated by NCBI nr blast, 1,745 by COG database and 1,829 by KEGG database. 109 potential virulence factors were annotated in strain ZJ0906 and 3 of which are potentially related to antibiotic resistance. Strain ZJ0906 genome is ∼55 kilobases longer than SH0165 genome, with an extra 211 predicted ORFs. VFDB, ARDB, and PAIDB blast searches showed that ZJ0906 and SH0165 shared a nearly identical panel of potential virulence factors, drug resistant genes and four PAI-like regions which showed high homology to Enterococcus, Escherichia and Salmonella. Synteny analysis showed that gene rearrangements are frequent between the two strains, which may lead to variations in pathogenicity and cross-protection among serovars. KEGG pathway analyses showed strain ZJ0906 shared similar metabolic pathways to strain SH0165. Molecular identification of these genomic elements and potential virulence factors pave the way to the better understanding of mechanisms underlying metabolic capabilities and pathogenicity of H. parasuis and prospective vaccine targets besides the widely used method of inactivated bacteria. [ABSTRACT FROM AUTHOR]

Emus (Dromaius novaehollandiae) are farmed for their oil for pharmaceutical and cosmetic uses. This emu pituitary expressed sequence tag study was undertaken to identify novel transcripts in the emu pituitary to propel their identification and functional studies. By mapping reads derived from the Roche 454 GS Junior pyrosequencer to 8 reference species (human, mouse, chicken, zebra finch, fruit fly, turkey, round worm, and Carolina anole lizard) from the UniGene database, a total of 81,788 reads (53,312 mapped reads) were obtained and assembled with Reference Sequence (RefSeq). We annotated 6,676 potential emu genes by referencing 7 species (excluding lizard) and identified 1,232 potential genes common among 3 species (hu-man, mouse, and chicken) with complete available ref-erence genomes. Gene Ontology analysis revealed 376 Gene Ontology terms showing, with the highest counts, their involvements in biological processes, metabolism, and cellular components. These potential genes were detected to associate with 20 pathways including mi-togen-activated protein kinase, insulin, neurotrophin signaling pathways, and carbohydrate digestion and absorption pathway. We also revealed a panel of tissue-specific genes including regulator of G-protein signaling protein (RGS), glucagon-like peptide receptor (GLPR), and growth hormone-inducible transmembrane pro-tein ( GHITM). Additionally, fatty acid binding protein (FABP), fatty acid desaturase (FAS), and stearoyl-co-enzyme A desaturase (SCD), key enzyme genes in fat metabolism, were found to be also expressed in emu pituitary. This expressed sequence tag study represents the first step in functional characterization of emu pi-tuitary gene expression and SNP identification for the improvement of fat production in the emu. [ABSTRACT FROM AUTHOR]

The placenta becomes one of the most diversified organs during placental mammal radiation. The main in vitro model for studying mouse trophoblast development is the 2D differentiation model of trophoblast stem cells, which is highly skewed to certain lineages and thus hampers systematic screens. Here, we established culture conditions for the establishment, maintenance, and differentiation of murine trophoblast organoids. Murine trophoblast organoids under the maintenance condition contain stem cell-like populations, whereas differentiated organoids possess various trophoblasts resembling placental ones in vivo. Ablation of Nubpl or Gcm1 in trophoblast organoids recapitulated their deficiency phenotypes in vivo , suggesting that those organoids are valid in vitro models for trophoblast development. Importantly, we performed an efficient CRISPR-Cas9 screening in mouse trophoblast organoids using a focused sgRNA (single guide RNA) library targeting G protein-coupled receptors. Together, our results establish an organoid model to investigate mouse trophoblast development and a practicable approach to performing forward screening in trophoblast lineages. [Display omitted] • Murine trophoblast organoids can be derived from placentae or trophoblast stem cells • Murine trophoblast organoids exhibit features of their placental trophoblast counterparts • Ablation of essential genes in trophoblast organoids recapitulates in vivo placental defects • Murine trophoblast organoids can be used for CRISPR-Cas9 screening Mao, Ye, Xu, Jiang et al. established murine trophoblast organoids, which can be used to model mouse placental development and perform high-throughput genetic screening in a dish. [ABSTRACT FROM AUTHOR]

Aims: Early gastric cardiac cancer (EGCC) has a low risk of lymph node metastasis with the potential for endoscopic therapy. We aimed to evaluate the short- and long-term outcomes of endoscopic submucosal dissection (ESD)-resected EGCCs in a large cohort of Chinese patients and compare endoscopic and clinicopathologic features between EGCC and early gastric non-cardiac cancer (EGNC). Methods: We retrospectively studied 512 EGCCs in 499 consecutive patients and 621 EGNCs in 555 consecutive patients between January 2011 and March 2018 at our center. We investigated clinicopathological characteristics of EGCC tumors, ESD treatment results, adverse events, and postresection patient survival. Results: Compared with EGNC patients, EGCC patients were significantly older (average age: 66 years versus 62 years, p < 0.001). The percentage of the gross 0–IIc pattern was higher in EGCCs (46.1%) than in EGNCs (41.5%), while the frequency of the 0–IIa pattern was lower in EGCCs (14.9%) than in EGNCs (22.4%) (p = 0.001). Compared with EGNCs, EGCCs showed smaller size, deeper invasion, fewer ulcerated or poorly differentiated tumors, but more cases with gastritis cystica profunda. The prevalence of ESD-related complications was higher in EGCCs (6.1%) than in EGNCs (2.3%) (p = 0.001). In EGCCs, the disease-specific survival rate was significantly higher in patients of the noncurative resection group with surgery (100%), compared with that (93.9%) without surgery (p < 0.001). Conclusion: Clinicopathological characteristics were significantly different between EGCCs and EGNCs. ESD is a safe and effective treatment option with favorable outcomes for patients with EGCC. Additional surgery improved survival in patients with noncurative ESD resection. [ABSTRACT FROM AUTHOR]

Aims: Early gastric cardiac cancer (EGCC) has a low risk of lymph node metastasis with the potential for endoscopic therapy. We aimed to evaluate the short- and long-term outcomes of endoscopic submucosal dissection (ESD)-resected EGCCs in a large cohort of Chinese patients and compare endoscopic and clinicopathologic features between EGCC and early gastric non-cardiac cancer (EGNC). Methods: We retrospectively studied 512 EGCCs in 499 consecutive patients and 621 EGNCs in 555 consecutive patients between January 2011 and March 2018 at our center. We investigated clinicopathological characteristics of EGCC tumors, ESD treatment results, adverse events, and postresection patient survival. Results: Compared with EGNC patients, EGCC patients were significantly older (average age: 66 years versus 62 years, p < 0.001). The percentage of the gross 0–IIc pattern was higher in EGCCs (46.1%) than in EGNCs (41.5%), while the frequency of the 0–IIa pattern was lower in EGCCs (14.9%) than in EGNCs (22.4%) (p = 0.001). Compared with EGNCs, EGCCs showed smaller size, deeper invasion, fewer ulcerated or poorly differentiated tumors, but more cases with gastritis cystica profunda. The prevalence of ESD-related complications was higher in EGCCs (6.1%) than in EGNCs (2.3%) (p = 0.001). In EGCCs, the disease-specific survival rate was significantly higher in patients of the noncurative resection group with surgery (100%), compared with that (93.9%) without surgery (p < 0.001). Conclusion: Clinicopathological characteristics were significantly different between EGCCs and EGNCs. ESD is a safe and effective treatment option with favorable outcomes for patients with EGCC. Additional surgery improved survival in patients with noncurative ESD resection. [ABSTRACT FROM AUTHOR]

Leptin resistance is a hallmark of obesity with unclear etiology. Celastrol, a compound found in the roots of the Tripterygium wilfordii and known to reduce endoplasmic reticulum (ER) stress, has recently emerged as a promising candidate to treat obesity by improving leptin sensitivity. However, the underlying neural mechanisms by which celastrol reduces obesity remain unclear. Using three different mouse models of obesity-diet-induced obesity (DIO), leptin receptor (LepR)-null, and melanocortin 4 receptor (MC4R)-null mice-in this study, we show that systemic celastrol administration substantially reduces food intake and body weight in MC4R-null comparable to DIO, proving the MC4R-independent antiobesity effect of celastrol. Body weight reduction was due to decreases in both fat and lean mass, and modest but significant body weight reduction was also observed in nonobese wild-type and LepR-null mice. Unexpectedly, celastrol upregulated proinflammatory cytokines without affecting genes involved in ER stress. Importantly, celastrol steadily increased sympathetic nerve activity to the brown fat and kidney with concordant increases of resting metabolic rate and arterial pressure. Our results suggest a previously unappreciated mechanism of action of celastrol in the regulation of energy homeostasis and highlight the need for careful consideration of its development as a safe antiobesity medication. [ABSTRACT FROM AUTHOR]

Silicon monoxide (SiO) is a promising anode material for lithium-ion batteries (LIBs) due to its relatively low volume change and superior cycling performance compared to silicon (Si). However, its low initial Coulombic efficiency (ICE) should be improved when the addition of SiO is higher than 5 wt% in graphite. Many prelithiation attempts have been made to improve its ICE, among which chemical prelithiation is widely used. However, the complex microstructures of prelithiated SiO (pre-SiO) hinder exploring the interconnection between microstructure and composition changes with its electrochemical performance. The size of Si nanodomains embedded in pre-SiO plays a crucial role in electrochemical performance. Herein, samples with different sizes of Si nanodomains are prepared via regulating the degree of prelithiation. Then the structure, composition evolutions and the size effect of Si nanodomains on the electrochemical performance are well investigated. The Si nanodomain size grows with the incremental prelithiation degree, leading to more capacity degradation. It is indicated that prelithiation promotes the growth of Si nanodomains and an appropriate Si nanodomain size of ∼10 nm is essential to retard volume expansion thus improving the cyclability. These results give fundamental insight into the pre-SiO for its future applications as the next-generation LIBs anodes. • Pre-SiO with different sizes of Si nanodomain were prepared via the Li/Si ratio. • The structure and composition content evolutions in pre-SiO were investigated. • The effect of Si nanodomain size on pre-SiO performance was investigated. • The appropriate size of Si nanodomain in pre-SiO boosts structural stability. [ABSTRACT FROM AUTHOR]

Sea urchins have long been used as research model organisms for developmental biology and evolutionary studies. Some of them are also important aquaculture species in East Asia. In this work, we report the construction of RAD-tag based high-density genetic maps by genotyping F1 interspecific hybrids derived from a crossing between a female sea urchin Strongylocentrotus nudus and a male Strongylocentrotus intermedius. With polymorphisms present in these two wild individuals, we constructed a female meiotic map containing 3,080 markers for S. nudus, and a male meiotic map for S. intermedius which contains 1,577 markers. Using the linkage maps, we were able to anchor a total of 1,591 scaffolds (495.9 Mb) accounting for 60.8% of the genome assembly of Strongylocentrotus purpuratus. A genome-wide scan resulted in the identification of one putative QTL for body size which spanned from 25.3 cM to 30.3 cM. This study showed the efficiency of RAD-Seq based high-density genetic map construction using F1 progenies for species with no prior genomic information. The genetic maps are essential for QTL mapping and are useful as framework to order and orientate contiguous scaffolds from sea urchin genome assembly. The integration of the genetic map with genome assembly would provide an unprecedented opportunity to conduct QTL analysis, comparative genomics, and population genetics studies. [ABSTRACT FROM AUTHOR]

Purpose: This study analyzed the clinicopathologic characteristics of typical medullary breast carcinoma (TMBC) in a cohort of Chinese patients. Methods: We conducted a retrospective review of clinical data including general information, pathologic results, treatment regimens, and patient survival in cases of TMBC diagnosed between February 2004 and April 2011. Results: A total of 117 patients were enrolled, with a median age of 52 years (range, 28∼92 years). Stage I and II disease accounted for 31.6% and 61.6% of the cases, respectively. Hormonal receptor negative disease (estrogen receptor negative, 68.4%; progestogen receptor negative, 86.3%) was more prevalent in this population. Human epidermal growth factor receptor-2 (HER-2) positivity was 20.5%, while equivocal and HER-2 negative cases represented 16.2% and 63.2% of the cohort. The triple-negative, luminal, and HER-2 overexpressing subtypes constituted 44.4%, 31.6%, and 15.4% of the cases, respectively. The various TMBC subtypes showed no differences regarding tumor size, rates of lymph node(s) metastasis, TNM staging, treatment regimens, and 2-year recurrence rates. However, patients with triple-negative disease were more likely to be younger, when compared to those with luminal disease (P = 0.002). At a median follow-up of 56 months (range, 2–112 months), the 2-year disease-free survival and overall survival rates were 99.1% and 98.2%, respectively. Conclusion: Early stage disease dominated the study cohort, and at two years after surgery, recurrence was extremely low. The heterogeneity of molecular subtypes was clearly shown, and no apparent differences were found among the clinicopathologic characteristics of the triple-negative, luminal, and HER-2 overexpressing subtypes. [ABSTRACT FROM AUTHOR]

In recent years, sea cucumber has become a favorite healthcare food due to its characteristic prevention of cardiovascular diseases, suppression of tumors, as well as enhancement of immunity. In order to screen the anti-tumoral proteins or peptides from sea cucumber (Apostichopus japonicus), its cDNA library was analyzed, and a disintegrin-like and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13)-like was found. ADAMTS13-like contains 10 thrombospondin 1 (TSP1) domains. Based on analysis of bioinformatics, the third TSP1 domain of this protein, which is further named Aj-Tspin, contains an arginine-glycine-aspartate (RGD) motif. Since our previous studies showed that the recombinant RGD-containing peptide from lampreys showed anti-tumoral activity, the third TSP1 domain of ADAMTS13-like was chosen to evaluate it's effect on tumor proliferation and metastasis, despite the fact it shares almost no homologue with disintegrins from other species. After artificial synthesis, its cDNA sequence, Aj-Tspin, which is composed of 56 amino acids, was subcloned into a pET23b vector and expressed as a recombinant Aj-Tspin (rAj-Tspin) in a soluble form with a molecular weight of 6.976 kDa. Through affinity chromatography, rAj-Tspin was purified as a single protein. Both anti-proliferation and immunofluorescence assays showed that rAj-Tspin suppressed the proliferation of Lewis lung carcinoma (LLC) cells through apoptosis. Adhesion assay also displayed that rAj-Tspin inhibited the adhesion of LLC cells to ECM proteins, including fibronectin, laminin, vitronectin and collagen. Lastly, rAj-Tspin also suppressed the migration and invasion of LLC cells across the filter in transwells. Thus, the above indicates that rAj-Tspin might act as a potential anti-tumoral drug in the future and could also provide information on the nutritional value of sea cucumber. [ABSTRACT FROM AUTHOR]

Background: Lycoris aurea, also called Golden Magic Lily, is an ornamentally and medicinally important species of the Amaryllidaceae family. To date, the sequencing of its whole genome is unavailable as a non-model organism. Transcriptomic information is also scarce for this species. In this study, we performed de novo transcriptome sequencing to produce the first comprehensive expressed sequence tag (EST) dataset for L. aurea using high-throughput sequencing technology. Methodology and Principal Findings: Total RNA was isolated from leaves with sodium nitroprusside (SNP), salicylic acid (SA), or methyl jasmonate (MeJA) treatment, stems, and flowers at the bud, blooming, and wilting stages. Equal quantities of RNA from each tissue and stage were pooled to construct a cDNA library. Using 454 pyrosequencing technology, a total of 937,990 high quality reads (308.63 Mb) with an average read length of 329 bp were generated. Clustering and assembly of these reads produced a non-redundant set of 141,111 unique sequences, comprising 24,604 contigs and 116,507 singletons. All of the unique sequences were involved in the biological process, cellular component and molecular function categories by GO analysis. Potential genes and their functions were predicted by KEGG pathway mapping and COG analysis. Based on our sequence analysis and published literatures, many putative genes involved in Amaryllidaceae alkaloids synthesis, including PAL, TYDC OMT, NMT, P450, and other potentially important candidate genes, were identified for the first time in this Lycoris. Furthermore, 6,386 SSRs and 18,107 high-confidence SNPs were identified in this EST dataset. Conclusions: The transcriptome provides an invaluable new data for a functional genomics resource and future biological research in L. aurea. The molecular markers identified in this study will provide a material basis for future genetic linkage and quantitative trait loci analyses, and will provide useful information for functional genomic research in future. [ABSTRACT FROM AUTHOR]

Clinical evidence suggests that poor persistence of chimeric antigen receptor-T cells (CAR-T) in patients limits therapeutic efficacy. Here, we designed a CAR with recyclable capability to promote in vivo persistence and to sustain antitumor activity. We showed that the engagement of tumor antigens induced rapid ubiquitination of CARs, causing CAR downmodulation followed by lysosomal degradation. Blocking CAR ubiquitination by mutating all lysines in the CAR cytoplasmic domain (CARKR) markedly repressed CAR downmodulation by inhibiting lysosomal degradation while enhancing recycling of internalized CARs back to the cell surface. Upon encountering tumor antigens, CARKR-T cells ameliorated the loss of surface CARs, which promoted their long-term killing capacity. Moreover, CARKR-T cells containing 4-1BB signaling domains displayed elevated endosomal 4-1BB signaling that enhanced oxidative phosphorylation and promoted memory T cell differentiation, leading to superior persistence in vivo. Collectively, our study provides a straightforward strategy to optimize CAR-T antitumor efficacy by redirecting CAR trafficking. • Tumor antigen encounter triggers CAR ubiquitination and downmodulation • Tumor antigen-induced CAR ubiquitination targets CARs for lysosomal degradation • CAR signaling in CAR-T cells expressing 4-1BB can be propagated in endosomes • Blocking CAR ubiquitination enhances endosomal CAR signaling and CAR-T persistence Chimeric antigen receptor-T cell therapy offers a promising approach for cancer immunotherapy, but poor CAR-T persistence in patients limits therapeutic efficacy. Li et al. investigated the trafficking of CARs during CAR-T cell activation and designed a recyclable CAR with enhanced persistence and sustained antitumor function. [ABSTRACT FROM AUTHOR]

Outbreaks in fish of motile Aeromonad septicemia (MAS) caused by Aeromonas hydrophila have caused a great concern worldwide. Here, for the first time, we provide two complete genomes of epidemic A. hydrophila strains isolated in China. To gain an insight into the pathogenicity of epidemic A. hydrophila, we performed comparative genomic analyses of five epidemic strains belonging to sequence type (ST) 251, together with the environmental strain ATCC 7966T. We found that the known virulence factors, including a type III secretion system, a type VI secretion system and lateral flagella, are not required for the high virulence of the ST251 clonal group. Additionally, our work identifies three utilization pathways for myo-inositol, sialic acid and L-fucose providing clues regarding the factors that underlie the epidemic and virulent nature of ST251 A. hydrophila. Based on the geographical distribution and biological resources of the ST251 clonal group, we conclude that ST251 is a high-risk clonal group of A. hydrophila which may be responsible for the MAS outbreaks in China and the southeastern United States. [ABSTRACT FROM AUTHOR]