DWRSeg: Rethinking Efficient Acquisition of Multi-scale Contextual Information for Real-time Semantic Segmentation

Many current works directly adopt multi-rate depth-wise dilated convolutions to capture multi-scale contextual information simultaneously from one input feature map, thus improving the feature extraction efficiency for real-time semantic segmentation. However, this design may lead to difficult access to multi-scale contextual information because of the unreasonable structure and hyperparameters. To lower the difficulty of drawing multi-scale contextual information, we propose a highly efficient multi-scale feature extraction method, which decomposes the original single-step method into two steps, Region Residualization-Semantic Residualization. In this method, the multi-rate depth-wise dilated convolutions take a simpler role in feature extraction: performing simple semantic-based morphological filtering with one desired receptive field in the second step based on each concise feature map of region form provided by the first step, to improve their efficiency. Moreover, the dilation rates and the capacity of dilated convolutions for each network stage are elaborated to fully utilize all the feature maps of region form that can be achieved.Accordingly, we design a novel Dilation-wise Residual (DWR) module and a Simple Inverted Residual (SIR) module for the high and low level network, respectively, and form a powerful DWR Segmentation (DWRSeg) network. Extensive experiments on the Cityscapes and CamVid datasets demonstrate the effectiveness of our method by achieving a state-of-the-art trade-off between accuracy and inference speed, in addition to being lighter weight. Without pretraining or resorting to any training trick, we achieve an mIoU of 72.7% on the Cityscapes test set at a speed of 319.5 FPS on one NVIDIA GeForce GTX 1080 Ti card, which exceeds the latest methods of a speed of 69.5 FPS and 0.8% mIoU. The code and trained models are publicly available

Metabolomics of a cell line-derived xenograft model reveals circulating metabolic signatures for malignant mesothelioma

Background Malignant mesothelioma (MM) is a rare and highly aggressive cancer. Despite advances in multidisciplinary treatments for cancer, the prognosis for MM remains poor with no effective diagnostic biomarkers currently available. The aim of this study was to identify plasma metabolic biomarkers for better MM diagnosis and prognosis by use of a MM cell line-derived xenograft (CDX) model. Methods The MM CDX model was confirmed by hematoxylin and eosin staining and immunohistochemistry. Twenty female nude mice were randomly divided into two groups, 10 for the MM CDX model and 10 controls. Plasma samples were collected two weeks after tumor cell implantation. Gas chromatography-mass spectrometry analysis was conducted. Both univariate and multivariate statistics were used to select potential metabolic biomarkers. Hierarchical clustering analysis, metabolic pathway analysis, and receiver operating characteristic (ROC) analysis were performed. Additionally, bioinformatics analysis was used to investigate differential genes between tumor and normal tissues, and survival-associated genes. Results The MM CDX model was successfully established. With VIP > 1.0 and P-value < 0.05, a total of 23 differential metabolites were annotated, in which isoleucine, 5-dihydrocortisol, and indole-3-acetamide had the highest diagnostic values based on ROC analysis. These were mainly enriched in pathways for starch and sucrose metabolism, pentose and glucuronate interconversions, galactose metabolism, steroid hormone biosynthesis, as well as phenylalanine, tyrosine and tryptophan biosynthesis. Further, down-regulation was observed for amino acids, especially isoleucine, which is consistent with up-regulation of amino acid transporter genes SLC7A5 and SLC1A3 in MM. Overall survival was also negatively associated with SLC1A5, SLC7A5, and SLC1A3. Conclusion We found several altered plasma metabolites in the MM CDX model. The importance of specific metabolic pathways, for example amino acid metabolism, is herein highlighted, although further investigation is warranted

Matrine induces cell cycle arrest and apoptosis in hepatocellular carcinoma cells via miR-122 mediated CG1/livin/survivin signal axis

Purpose: To study the impact of matrine on cell cycle and apoptotic changes in hepatoma cells, and the mechanism involved. Methods: Human hepatoma cell line HepG2 was treated with different concentrations of matrine. The blank control cells were maintained in 1640 medium only. The influence of matrine on proliferative ability was determined with 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) method. Flow cytometry was used to determine its effect on cell cycle and apoptosis; RT-PCR (reverse transcription-polymerase chain reaction) was applied to assay the mRNA expressions of miR-122, cyclin G1 (CG1), livin and survivin mRNA, while the protein expressions of CG1, livin and surviving were assayed by Western blotting. Results: Matrine time- and dose-dependently suppressed the proliferative capacity of the cells. At a concentration of 0.5 mg/mL, matrine had no significant effect on the cell cycle. However, 1.0 mg/mL matrine blocked the cell cycle in G1 phase, while 1.5 mg/mL matrine blocked HepG2 cells in G2/M phase (p &lt; 0.05). Moreover, matrine induced apoptosis in HepG2 cells, and markedly downregulated the expressions of miR-122 concentration- time-reliantly (p &lt; 0.05). In addition, matrine markedly and concentration-dependently reduced mRNA and protein expression levels of CG1, livin and survivin, with the strongest inhibitory effect at a level of 1.5 mg/mL. Conclusion: Matrine induces cell cycle block and apoptotic changes in hepatoma cells through a mechanism related to regulation of the CG1/livin/survivin signal axis mediated by miR-122. Matrine may be a potential treatment for liver cancer. However, clinical trials are needed to confirm this potential

Total Synthesis and Chemoproteomics Connect Curcusone Diterpenes with Oncogenic Protein BRAT1

Natural products are an indispensable source of lifesaving medicine, but natural product-based drug discovery often suffers from scarce natural supply and unknown mode of action. The study and development of anticancer curcusone diterpenes fall into such a dilemma. Meanwhile, many biologically-validated disease targets are considered “undruggable” due to the lack of enzymatic activity and/or predicted small molecule binding sites. The oncogenic BRCA1-associated ATM activator 1 (BRAT1) belongs to such an “undruggable” category. Here, we report our synthetic and chemoproteomics studies of the curcusone diterpenes that culminate in an efficient total synthesis and the identification of BRAT1 as a cellular target. We demonstrate for the first time that BRAT1 can be inhibited by a small molecule (curcusone D), resulting in impaired DNA damage response, reduced cancer cell migration, potentiated activity of the DNA damaging drug etoposide, and other phenotypes similar to BRAT1 knockdown

ZIF-derived carbon nanoarchitecture as a bifunctional pH-universal electrocatalyst for energy-efficient hydrogen evolution

Development of nonprecious metal-based electrocatalysts supporting hydrogen evolution reaction (HER) in the entire pH range has gained significant importance for harvesting green and renewable energy. Herein, we developed a novel electrocatalyst based on 3D carbon nanoarchitecture hybrid, which consists of CoP nanoparticles (CoP NPs) embedded into N-doped carbon nanotubes (NCNT), grafted on carbon polyhedron (CoP/NCNT-CP) that was prepared by carbonization and low-temperature phosphatization treatment of cobalt-based zeolite imidazole framework (ZIF). Benefiting from the strong synergistic effect and unique 3D structure, the CoP/NCNT-CP hybrid loaded on Ni foam exhibited excellent electrocatalytic HER performance in base with a low overpotential of 165 mV at a current density of 10 mA cm-2, which is competitive with the previously reported Co-based hybrid electrocatalysts. Furthermore, the CoP/NCNT-CP also demonstrated high HER electrocatalytic activities in both neutral and acidic conditions with the overpotentials of 203 and 305 mV at the current density of 10 mA cm-2. Additionally, the bifunctional CoP/NCNT-CP electrode simultaneously acted as an anode for hydrazine oxidation reaction (HzOR) and a cathode for HER. Excellent catalytic performance was demonstrated in base conditions with a low cell potential of 0.89 V at 10 mA cm-2, which was much lower than the voltage of overall water splitting (1.91 V) at the same current density.</p

Comparative proteomics reveals the physiological differences between winter tender shoots and spring tender shoots of a novel tea (Camellia sinensis L.) cultivar evergrowing in winter

Abstract Background A recently discovered tea [Camellia sinensis (L.) O. Kuntze] cultivar can generate tender shoots in winter. We performed comparative proteomics to analyze the differentially accumulated proteins between winter and spring tender shoots of this clonal cultivar to reveal the physiological basis of its evergrowing character during winter. Results We extracted proteins from the winter and spring tender shoots (newly formed two leaves and a bud) of the evergrowing tea cultivar “Dongcha11” respectively. Thirty-three differentially accumulated high-confidence proteins were identified by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF / TOF MS). Among these, 24 proteins had increased abundance while nine showed were decreased abundance in winter tender shoots as compared with the spring tender shoots. We categorized the differentially accumulated proteins into eight critical biological processes based on protein function annotation including photosynthesis, cell structure, protein synthesis & destination, transporters, metabolism of sugars and polysaccharides, secondary metabolism, disease/defense and proteins with unknown functions. Proteins with increased abundance in winter tender shoots were mainly related to the processes of photosynthesis, cytoskeleton and protein synthesis, whereas those with decreased abundance were correlated to metabolism and the secondary metabolism of polyphenolic flavonoids. Biochemical analysis showed that the total contents of soluble sugar and amino acid were higher in winter tender shoots while tea polyphenols were lower as compared with spring tender shoots. Conclusions Our study suggested that the simultaneous increase in the abundance of photosynthesis-related proteins rubisco, plastocyanin, and ATP synthase delta chain, metabolism-related proteins eIF4 and protease subunits, and the cytoskeleton-structure associated proteins phosphatidylinositol transfer protein and profilin may be because of the adaptation of the evergrowing tea cultivar “Dongcha11” to low temperature and light conditions. Histone H4, Histone H2A.1, putative In2.1 protein and protein lin-28 homologs may also regulate the development of winter shoots and their response to adverse conditions

L'Auto-vélo : automobilisme, cyclisme, athlétisme, yachting, aérostation, escrime, hippisme / dir. Henri Desgranges

26 avril 19321932/04/26 (A33,N11455)

The Msi1-mTOR pathway drives the pathogenesis of mammary and extramammary Paget's disease.

Mammary and extramammary Paget's Diseases (PD) are a malignant skin cancer characterized by the appearance of Paget cells. Although easily diagnosed, its pathogenesis remains unknown. Here, single-cell RNA-sequencing identified distinct cellular states, novel biomarkers, and signaling pathways&nbsp;-&nbsp;including mTOR, associated with extramammary PD. Interestingly, we identified MSI1 ectopic overexpression in basal epithelial cells of human PD skin, and show that Msi1 overexpression in the epidermal basal layer of mice phenocopies human PD at histopathological, single-cell and molecular levels. Using this mouse model, we identified novel biomarkers of Paget-like cells that translated to human Paget cells. Furthermore, single-cell trajectory, RNA velocity and lineage-tracing analyses revealed a putative keratinocyte-to-Paget-like cell conversion, supporting the in situ transformation theory of disease pathogenesis. Mechanistically, the Msi1-mTOR pathway drives keratinocyte-Paget-like cell conversion, and suppression of mTOR signaling with Rapamycin significantly rescued the Paget-like phenotype in Msi1-overexpressing transgenic mice. Topical Rapamycin treatment improved extramammary PD-associated symptoms in humans, suggesting mTOR inhibition as a novel therapeutic treatment in PD

The Msi1-mTOR pathway drives the pathogenesis of mammary and extramammary Paget's disease.

Mammary and extramammary Paget's Diseases (PD) are a malignant skin cancer characterized by the appearance of Paget cells. Although easily diagnosed, its pathogenesis remains unknown. Here, single-cell RNA-sequencing identified distinct cellular states, novel biomarkers, and signaling pathways&nbsp;-&nbsp;including mTOR, associated with extramammary PD. Interestingly, we identified MSI1 ectopic overexpression in basal epithelial cells of human PD skin, and show that Msi1 overexpression in the epidermal basal layer of mice phenocopies human PD at histopathological, single-cell and molecular levels. Using this mouse model, we identified novel biomarkers of Paget-like cells that translated to human Paget cells. Furthermore, single-cell trajectory, RNA velocity and lineage-tracing analyses revealed a putative keratinocyte-to-Paget-like cell conversion, supporting the in situ transformation theory of disease pathogenesis. Mechanistically, the Msi1-mTOR pathway drives keratinocyte-Paget-like cell conversion, and suppression of mTOR signaling with Rapamycin significantly rescued the Paget-like phenotype in Msi1-overexpressing transgenic mice. Topical Rapamycin treatment improved extramammary PD-associated symptoms in humans, suggesting mTOR inhibition as a novel therapeutic treatment in PD