Several variants of the plasmid-carried tigecycline resistance gene cluster,
, have been identified. This study characterized another novel variant,
, located on the chromosome of ...environmental-origin Pseudomonas mendocina. TMexC6D6-TOprJ1 mediates resistance to multiple drugs, including tigecycline. The promoter activity of
and negative transcriptional repression by the upstream regulator tnfxB6 are crucial for the expression of
.
was found in the plasmids or chromosomes of different Pseudomonas species from six countries. Two genetic backgrounds, class 1 integrons and
-carrying integrase units, were found adjacent to the
gene cluster and might mediate the transfer of this novel efflux pump gene cluster in Pseudomonas. Further phylogenetic analysis revealed Pseudomonas as the major reservoir of
variants, warranting closer monitoring in the future.
Tigecycline is one of the treatment options for serious infections caused by multidrug-resistant bacteria, and tigecycline resistance has gained extensive attention. The emergence of a transferable tigecycline resistance efflux pump gene cluster,
, severely challenged the efficiency of tigecycline. In this study, we identified another novel
variant,
, which could confer resistance to multiple classes of antibiotics, including tigecycline. Although
was found only in Pseudomonas species,
might spread to
hosts via mobile genetic elements resembling those of other
variants, compromising the therapeutic strategies. Meanwhile, novel transferable
variants are constantly emerging and mostly exist in Pseudomonas spp., indicating Pseudomonas as the important hidden reservoir and origin of
variants. Continuous monitoring and investigations of
are urgent to control its spread.
Progestin and adipoQ receptor 5 (PAQR5) affects the development of various malignancies and is specifically expressed in kidney. However, the role of PAQR5 in renal carcinoma remains unclear. We ...assessed the state of PAQR5 expression in kidney renal clear cell carcinoma (KIRC) by The Cancer Genome Atlas and Gene Expression Omnibus datasets. Moreover, immunohistochemistry was performed to observe the expressions of PAQR5 protein in tumor tissues. The relationships between PAQR5 expression and clinical characteristics were investigated by UALCAN. Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier plotter were used to analyze the effect of PAQR5 expression levels on overall survival and relapse-free survival (RFS). The re lationships between clinical characteristics and survival were also evaluated by univariate and multifactorial Cox regression. Gene Ontology term analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and gene set enrichment analysis were performed on PAQR5 to explain the enrichment pathways and functions. Protein and protein interactions were explained by GeneMANIA and STRING. We also explored the relevance of PAQR5 to tumor immune cell infiltration and immunomodulatory molecules by TIMER and GEPIA. Finally, we explored the correlation of PAQR5 with the pathway proteins STATs, HIF-1α, and mTOR using the GSE40435 dataset. PAQR5 expression was low in KIRC and correlated significantly with clinical characteristics including cancer stage, tumor grade, and nodal metastasis status. Low PAQR5 expression was significantly associated with poorer survival. Cox regression analysis indicated that upregulation of PAQR5 was an independent factor for a good prognosis of KIRC. PAQR5 downregulation was associated mainly with STAT3 target upregulation, tumorigenesis, and poor differentiation. PAQR5 expression also correlated positively with B cells, neutrophils, macrophages, and dendritic cells and negatively with the infiltration of FOXP3
+
Treg cells and the immune checkpoint molecules PD-1, CTLA4, and LAG3. Moreover, PAQR5 expression in KIRC was negatively correlated with the pathway proteins STAT1/2/3/4/5A, HIF-1α, and mTOR. PAQR5 is an excellent predictor of KIRC prognosis and may be a potential molecular therapeutic target.
Hotspot is a ubiquitous phenomenon in micro/nanoscale chips. Here, it is found that the thermal conductivity is not a constant in such a homogeneous system. The hotspots in homogeneous 2D disk/3D ...sphere and graphene disk are studied based on phonon Boltzmann transport equation. Instead a constant value, a graded thermal conductivity is observed even if the system size is fixed. The mechanisms of phonon scattering are analyzed. It is found that for a system with fixed size, the graded thermal conductivity is predictable as long as there is not sufficient phonon scattering, which is independent on material properties, dimensions or system size. This work may shed light on both theoretical and experimental studies on heat dissipation.
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•It demonstrates a fundamental physical understanding of thermal transport of hotspots.•Hotspots in a 2D disk, 3D ball, and graphene disk (up to 20 μm) are studied by phonon Boltzmann transport equation.•It is found that the thermal conductivity is graded diverging from the hotspot to the outer, which is much different from conventional understanding.•The graded thermal conductivity comes from insufficient phonon scatterings, which are independent of the material, dimension, or system size.
Imazethapyr (IM) is an acetolactate synthase (ALS)-inhibiting herbicide that has been widely used in recent years. However, IM spraying can lead to the accumulation of herbicide residues in leaves. ...Here, we determined the effects of IM spraying on the plant growth and leaf surface microbial communities of Arabidopsis thaliana after 7 and 14 days of exposure. The results suggested that IM spraying inhibited plant growth. Fresh weight decreased to 48% and 26% of the control value after 7 and 14 days, respectively, of 0.035 kg/ha IM exposure. In addition, anthocyanin content increased 9.2-fold and 37.2-fold relative to the control content after 7 and 14 days of treatment, respectively. Furthermore, IM spraying destroyed the cell structures of the leaves, as evidenced by increases in the number of starch granules and the stomatal closure rate. Reductions in photosynthetic efficiency and antioxidant enzyme activity were observed after IM spraying, especially after 14 days of exposure. The diversity and evenness of the leaf microbiota were not affected by IM treatment, but the composition of community structure at the genus level was altered by IM spraying. Imazethapyr application increased the abundance of Pseudomonas, a genus that includes species pathogenic to plants and humans, indicating that IM potentially increased the abundance of pathogenic bacteria on leaves. Our findings increase our understanding of the relationships between herbicide application and the microbial community structures on plant leaves, and they provide a new perspective for studying the ecological safety of herbicide usage.
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Mesoporous TiO
2
hollow microspheres (HTM) composed of irregularly arranged nanospheres were prepared through a one-pot template-free solvothermal way based on the aldol condensation reaction of ...acetylacetone. The synthesized hollow TiO
2
microspheres were investigated by a series of characterizations. Images of FE-SEM and TEM demonstrate that the surface of TiO
2
hollow microsphere with a diameter of 1.5 µm are mesoporous and constructed with 150 nm TiO
2
nanospheres. The mesoporous shell of the hollow microspheres is about 110 nm in thickness. XRD pattern shows the prepared samples are anatase phase. UV–Vis spectrum indicates that excellent light scattering ability of the prepared sample. The DSSCs using mesoporous TiO
2
hollow microspheres as the top scattering layer exhibits the improvement of short-circuit current density (J
sc
) and conversion efficiency (
η
) of 6.63%, while the benchmarked P
25
photoanode is only 5.09%, showing 30% increase in the energy conversion efficiency.
In one-dimensional (1D) metallic systems, the diverging electron susceptibility and electron-phonon coupling collaboratively drive the electrons into a charge density wave (CDW) state. However, a ...strictly 1D system is unstable against perturbations, whose effect on CDW order requires clarification ideally with altered coupling to surroundings. Here, we fabricate such a system with nanowires ofMo6Se6bundles, which are either attached to edges of monolayerMoSe2or isolated freely, by postannealing the preformedMoSe2. Using scanning tunneling microscopy, we visualize charge modulations and CDW gaps with prominent coherent peaks in the edge-attached nanowires. Astonishingly, the CDW order becomes suppressed in the isolated nanowires, showing CDW correlation gaps without coherent peaks. The contrasting behavior, as revealed with theoretical modeling, is interpreted as the effect of phason polarons on the 1D CDW state. Our work elucidates a possibly unprecedented many-body effect that may be generic to strictly 1D system but undermined in a quasi-1D system.
Animal disease models are necessary in medical research, and an appropriate animal model is of great importance for studies about the prevention or treatment of cancer. The most important thing in ...the selection of animal models is to consider the similarity between animals and humans. The tree shrew (
) is a squirrel-like mammal which placed in the order Scandentia. Whole-genome sequencing has revealed that tree shrews are extremely similar to primate and humans than to rodents, with many highly conserved genes, which makes the data from studies that use tree shrews as models more convincing and the research outcomes more easily translatable. In tumor research, tree shrews are often used as animal models for hepatic and mammary cancers. As research has progressed, other types of tree shrew tumor models have been developed and exhibit clinical manifestations similar to those of humans. Combining the advantages of both rodents and primates, the tree shrew is expected to be the most powerful animal model for studying tumors.
Vacuolar protein sorting 34 (Vps34) complexes, the class III PtdIns3 kinase, specifically phosphorylate the D3 position of PtdIns to produce PtdIns3P. Vps34 is involved in the control of multiple key ...intracellular membrane trafficking pathways including endocytic sorting and autophagy. In mammalian cells, Vps34 interacts with Beclin 1, an ortholog of Atg6 in yeast, to regulate the production of PtdIns3P and autophagy. We show that Vps34 is phosphorylated on Thr159 by Cdk1, which negatively regulates its interaction with Beclin 1 during mitosis. Cdk5/p25, a neuronal Cdk shown to play a role in Alzheimer's disease, can also phosphorylate Thr159 of Vps34. Phosphorylation of Vps34 on Thr159 inhibits its interaction with Beclin 1. We propose that phosphorylation of Thr159 in Vps34 is a key regulatory mechanism that controls the class III PtdIns3 kinase activity in cell-cycle progression, development, and human diseases including neurodegeneration and cancers.
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▸ Vps34 is phosphorylated by Cdk1 during mitosis and upon Cdk5 activation ▸ Phosphorylation of Vps34 by Cdks leads to inhibition of its lipid kinase activity ▸ Phosphorylation of T159 on Vps34 interferes its binding with Beclin 1, and T159A Vps34 mutant is hyperactive in its lipid kinase activity ▸ T668 of Vps34 is required for its lipid kinase activity
Brain metastases represent a major cause of mortality among patients with breast cancer, and few effective targeted treatment options are currently available. Development of new biomarkers and ...therapeutic targets for breast cancer brain metastases (BCBM) is therefore urgently needed. In this study, we compared the gene expression profiles of the brain metastatic cell line MDA-MB-231-BR (231-BR) and its parental MDA-MB-231, and identified a total of 84 genes in the primary screening through a series of bioinformatic analyses, including construction of protein-protein interaction (PPI) networks by STRING database, identification of hub genes by applying of MCODE and Cytohubba algorithms, identification of leading-edge subsets of Gene Set Enrichment Analysis (GSEA), and identification of most up-regulated genes. Eight genes were identified as candidate genes due to their elevated expression in brain metastatic 231-BR cells and prognostic values in patients with BCBM. Then we knocked down the eight individual candidate genes in 231-BR cells and evaluated their impact on cell migration through a wound-healing assay, and four of them (KRT19, FKBP10, GSK3B and SPANXB1) were finally identified as key genes. Furthermore, the expression of individual key genes showed a correlation with the infiltration of major immune cells in the brain tumor microenvironment (TME) as analyzed by Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA), suggesting possible roles of them in regulation of the tumor immune response in TME. Therefore, the present work may provide new potential biomarkers for BCBM. Additionally, using GSEA, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Enrichment Analysis, we determined the top enriched cellular functions or pathways in 231-BR cells, which may help better understand the biology governing the development and progression of BCBM.
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