A Unique ATPase, ArtR (PA4595), Represses the Type III Secretion System in Pseudomonas aeruginosa

Pseudomonas aeruginosa is an important human pathogen which uses the type III secretion system (T3SS) as a primary virulence factor to establish infections in humans. The results presented in this report revealed that the ATP-binding protein PA4595 (named ArtR, a Regulator that is an ATP-activated Repressor of T3SS) represses T3SS expression in P. aeruginosa. The expression of T3SS genes, including exoS, exoY, exoT, exsCEBA, and exsD-pscB-L, increased significantly when artR was knockout. The effect of ArtR on ExsA is at the transcriptional level, not at the translational level. The regulatory role and cytoplasm localization of ArtR suggest it belongs to the REG sub-family of ATP-binding cassette (ABC) family. Purified GST-tagged ArtR showed ATPase activity in vitro. The conserved aspartate residues in the dual Walker B motifs prove to be essential for the regulatory function of ArtR. The regulation of T3SS by ArtR is unique, which does not involve the known GacS/A-RsmY/Z-RsmA-ExsA pathway or Vfr. This is the first REG subfamily of ATP-binding cassette that is reported to regulate T3SS genes in bacteria. The results specify a novel player in the regulatory networks of T3SS in P. aeruginosa

Comprehensive analysis of the prognosis and immune effect of the oncogenic protein Four Jointed Box 1

BackgroundThe Four Jointed Box 1 (FJX1) gene has been implicated in the upregulation of various cancers, highlighting its crucial role in oncology and immunity. In order to better understand the biological function of FJX1 and identify new immunotherapy targets for cancer, we conducted a comprehensive analysis of this gene.MethodsWe analyzed the expression profiles and prognostic value of FJX1 using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). Copy number alterations (CNAs), mutations, and DNA methylation were analyzed through cBioPortal. The Immune Cell Abundance Identifier (ImmuCellAI) was used to examine the correlation between FJX1 expression and immune cell infiltration. The relationship between FJX1 expression and immune-related genes and immunosuppressive pathway-related genes was analyzed using The Tumor Immune Estimation Resource version 2 (TIMER2). Tumor mutational burden (TMB) and microsatellite instability (MSI) were obtained from TCGA pan-cancer data. The effect of immunotherapy and the IC50 were assessed using IMvigor210CoreBiologies and Genomics For Drug Sensitivity in Cancer (GDSC). Finally, we evaluated the impact of FJX1 on colon cancer cell proliferation and migration through in vitro functional experiments.ResultsOur study indicated that FJX1 expression was high in most cancers and was significantly associated with poor prognosis. High FJX1 expression was also linked to significant alterations in CNA, DNA methylation, TMB, and MSI. Positive correlations were found between FJX1 expression and tumor-associated macrophages (TAMs) and with immune-related genes such as TGFB1 and IL-10 and immunosuppressive pathway-related genes such as TGFB1 and WNT1. On the other hand, FJX1 expression showed a negative relationship with CD8+ T cells. Furthermore, high FJX1 expression led to reduced effectiveness of immunotherapy and drug resistance. In colon cancer cells, FJX1 knockdown was found to decrease cell proliferation and migration.ConclusionOur research findings demonstrate that FJX1 is a new prognostic factor with a significant role in tumor immunity. Our results highlight the importance of further exploring the potential of targeting FJX1 as a therapeutic strategy in cancer

α1A-Adrenergic Receptor Induces Activation of Extracellular Signal-Regulated Kinase 1/2 through Endocytic Pathway

G protein-coupled receptors (GPCRs) activate mitogen-activated protein kinases through a number of distinct pathways in cells. Increasing evidence has suggested that endosomal signaling has an important role in receptor signal transduction. Here we investigated the involvement of endocytosis in α1A-adrenergic receptor (α1A-AR)-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2). Agonist-mediated endocytic traffic of α1A-AR was assessed by real-time imaging of living, stably transfected human embryonic kidney 293A cells (HEK-293A). α1A-AR was internalized dynamically in cells with agonist stimulation, and actin filaments regulated the initial trafficking of α1A-AR. α1A-AR-induced activation of ERK1/2 but not p38 MAPK was sensitive to disruption of endocytosis, as demonstrated by 4°C chilling, dynamin mutation and treatment with cytochalasin D (actin depolymerizing agent). Activation of protein kinase C (PKC) and C-Raf by α1A-AR was not affected by 4°C chilling or cytochalasin D treatment. U73122 (a phospholipase C [PLC] inhibitor) and Ro 31–8220 (a PKC inhibitor) inhibited α1B-AR- but not α1A-AR-induced ERK1/2 activation. These data suggest that the endocytic pathway is involved in α1A-AR-induced ERK1/2 activation, which is independent of Gq/PLC/PKC signaling

Relationship Between the Built Environment and the Location Choice of High-Tech Firms: Evidence from the Pearl River Delta

With the transition in the regional development discourse to knowledge- and innovation-based economics, the cultivation of innovation capacity has gained importance as an initiative to enhance regional sustainability and has emerged as a policy goal. An understanding of the formation of innovation clusters is critical to the cultivation of regional innovation capabilities. Except for the location and regional development conditions' factors, researchers emphasize a built environment's role in the formation of innovation clusters. Based on the spatial database of 12,516 high-tech firms in 2017 in the Pearl River Delta (PRD), this study developed a conceptual framework for the built environment. The framework comprises living, service, perceptual, industrial, and physical aspects. The direction and intensity of the correlation between built environment factors and high-tech firms are discussed using the spatial regression model and geographical detector (GD) technique. The results show a highly concentrated spatial distribution pattern of high-tech firms in the PRD. A significant county-level spatial autocorrelation is revealed through Moran's I. According to the model, we determine the positive impacts of technology support, transport infrastructure, and living service levels on the agglomeration of high-tech firms as well as the negative impact of the public service level. The GD's result demonstrates different levels of impact intensity of built environmental factors. We argue that a comprehensive understanding of the influence of built environment factors on innovation agglomeration will help policymakers develop targeted policies to foster local innovation capabilities and promote sustainable regional development

Microstructure and Friction Properties of AlCrTiVNb_x High-Entropy Alloys via Annealing Manufactured by Vacuum Arc Melting

To enhance the friction and wear properties of alloys, AlCrTiVNbx high-entropy alloys (HEAs) with various Nb contents were prepared using the arc melting technique and then annealed at 1000 °C for 2 h. The microstructure and hardness changes in the AlCrTiVNbx (x = 0.3, 0.4, and 0.5) HEAs after casting and annealing were studied via scanning electron microscopy, X-ray diffractometry, optical microscopy and the Vickers hardness test. The MFT-EC400 ball disc reciprocating friction and wear tester was used to investigate the wear resistance of the HEAs before and after annealing. The results show that the annealed AlCrTiVNbx HEAs changed from a single-phase structure to a multi-phase structure, and the content of the face-center cubic (FCC) phase and hexagonal close-packed (HCP) phase further increases with the increase in Nb content. The hardness value of the annealed HEAs is greatly enhanced compared with the casting state, and the hardness of the Nb0.5 HEA is increased from 543 HV to 725 HV after annealing. The wear resistance of the alloys after the annealing treatment is also greatly improved, among which Nb0.5 has the best wear resistance. The average friction coefficient of Nb0.5 is 0.154 and the wear rate is 2.117 × 10−5 mm3/(N·m). We believe that the precipitation strengthening after the annealing treatment and the lubrication effect of the FCC phase are the reasons for the significant improvement in wear resistance. The morphology of the samples indicates that the wear mechanism of the alloy includes adhesive wear, abrasive wear and a certain degree of oxidation wear

Understanding the graphene-polymer interfacial mechanical behavior via coarse-grained modeling

Understanding the interfacial behavior of graphene-polymer nanocomposite is a long-standing endeavor to gain deep insight into the mechanical properties of engineered structural materials. In this study, we implement the ‘hard’ cutoff scheme to develop a 4-1 mapping coarse-grained graphene (CGGr) model and the corresponding CG potential TersoffCG(4-1), which faithfully reproduces the honeycomb structure (bond length and angle) and mechanical properties of the graphene sheet compared to experimental results. Taking the poly(methyl methacrylate) (PMMA) and graphene sheet as a representative composite system, we establish a predictive CG modeling framework to study the interfacial behavior at a molecular level. By performing the rate-dependent interfacial separation simulations, our results reveal that lower separation velocity and thicker flexible layer can facilitate the craze fibrils formation and further enhance the toughness of the composite, which attribute to the adequate response of polymer to the graphene under lower velocity and more polymers that potentially to form fibrils under thicker flexible layer. Our work demonstrates the efficacy of TersoffCG(4-1) potential in understanding the interfacial mechanical behavior of graphene-polymer nanocomposite, offering an effective modeling strategy for performance improvement by designing the interfaces.</p

Screen sand retaining precision optimization experiment and a new empirical design model

In the design of sand retaining precision, the existing design methods consider unilateral factors or have limited applicability. A series of experimental tests for screen sand retaining precision optimization were performed. An empirical model was worked out by experiment results fitting. The experimental tests were performed using screen evaluation experimental apparatus with 35 types of formation sand samples and 9 types of screen samples. For all sand samples with different sizes, the optimum sand retaining precisions were determined by calculating the sand-passed ratios and flow capacity index under different sand retaining precisions. The experiment results were fitted, and a new model was put forward to design reasonable screen precision for a given formation sand, considering the median size, the characteristic size of fine composition and uniformity coefficient of the sand and real production condition. The model has been applied in more than 20 wells and the effect is very good. The model considers most important factors affecting sand control effect and has excellent adaptability. And the model provides an effective method to optimize the screen precision without the need of performing lots of experiment tests and is easy to be used. Key words: mechanical screen pipe, sand retaining precision, design optimization, sand retention experiment, sand contro

88

This report chronicles the process of producing the video drama, 88. The drama is a 24- minute short video produced by a student group, Ba Gua Production, as its final-year project done under the supervision of Ms Nikki Draper.Bachelor of Communication Studie