Determination of the mimic epitope of the M-like protein adhesin in swine Streptococcus equi subsp. zooepidemicus

<p>Abstract</p> <p>Background</p> <p>The M-like protein, also known as SzP, is expressed on the surface of <it>Streptococcus equi </it>subsp. z<it>ooepidemicus </it>(<it>S</it>. z<it>ooepidemicus</it>). Previous studies demonstrated that SzP is similar to M protein of group A <it>Streptococcus </it>in the structure and characteristics of antiphagocytosis. The M protein is an adhesin that can bind to the host cells, however it is not known whether the SzP of <it>S</it>. z<it>ooepidemicus </it>also functions as an adhesin. We conducted an investigation to determine SzP as an adhesin, and one SzP epitope was identified to be responsible for mediating binding to HEp-2 cells.</p> <p>Methods</p> <p>The gene encoding SzP was expressed in <it>E. coli</it>, and the purified recombinant SzP (rSzP) was recognized by rabbit anti-<it>S</it>. z<it>ooepidemicus </it>antibodies using immunoblot. Furthermore, the adherence of <it>S</it>. z<it>ooepidemicus </it>to HEp-2 cells was inhibited by anti-rSzP antibodies in a dose-dependent manner. We employed a random 12-peptide phage display library for screening of immunodominant mimics of the SzP, which were recognized by an anti-SzP specific monoclonal antibody (mAb 2C8). Initial positive phage clones were identified by ELISA, followed by assays to determine the adherence-inhibiting ability of the peptide.</p> <p>Results</p> <p>Ten out of fourteen selected positive clones showed high reactivity that effectively inhibited the binding of mAb 2C8 to rSzP. The motif XSLSRX was highly conserved among six of the ten clones.</p> <p>Conclusion</p> <p>Collectively, our findings suggest that the motif XSLSRX may represent an immunodominant mimic epitope of the SzP of <it>S</it>. z<it>ooepidemicus </it>strain ATCC 35246, and that the same epitope may be used to mediate SzP binding to HEp-2 cells.</p

CSC-Unet: A Novel Convolutional Sparse Coding Strategy Based Neural Network for Semantic Segmentation

It is a challenging task to accurately perform semantic segmentation due to the complexity of real picture scenes. Many semantic segmentation methods based on traditional deep learning insufficiently captured the semantic and appearance information of images, which put limit on their generality and robustness for various application scenes. In this paper, we proposed a novel strategy that reformulated the popularly-used convolution operation to multi-layer convolutional sparse coding block to ease the aforementioned deficiency. This strategy can be possibly used to significantly improve the segmentation performance of any semantic segmentation model that involves convolutional operations. To prove the effectiveness of our idea, we chose the widely-used U-Net model for the demonstration purpose, and we designed CSC-Unet model series based on U-Net. Through extensive analysis and experiments, we provided credible evidence showing that the multi-layer convolutional sparse coding block enables semantic segmentation model to converge faster, can extract finer semantic and appearance information of images, and improve the ability to recover spatial detail information. The best CSC-Unet model significantly outperforms the results of the original U-Net on three public datasets with different scenarios, i.e., 87.14% vs. 84.71% on DeepCrack dataset, 68.91% vs. 67.09% on Nuclei dataset, and 53.68% vs. 48.82% on CamVid dataset, respectively

The identification and characterization of nucleic acid chaperone activity of human enterovirus 71 nonstructural protein 3AB

AbstractHuman enterovirus 71 (EV71) belongs to the genus Enterovirus in the family Picornaviridae and has been recognized as one of the most important pathogens that cause emerging infectious disease. Despite of the importance of EV71, the nonstructural protein 3AB from this virus is little understood for its function during EV71 replication. Here we expressed EV71 3AB protein as recombinant protein in a eukaryotic expression system and uncovered that this protein possesses a nucleic acid helix-destabilizing and strand annealing acceleration activity in a dose-dependent manner, indicating that EV71 3AB is a nucleic acid chaperone protein. Moreover, we characterized the RNA chaperone activity of EV71 3AB, and revealed that divalent metal ions, such as Mg2+ and Zn2+, were able to inhibit the RNA helix-destabilizing activity of 3AB to different extents. Moreover, we determined that 3B plus the last 7 amino acids at the C-terminal of 3A (termed 3B+7) possess the RNA chaperone activity, and five amino acids, i.e. Lys-80, Phe-82, Phe-85, Tyr-89, and Arg-103, are critical and probably the active sites of 3AB for its RNA chaperone activity. This report reveals that EV71 3AB displays an RNA chaperone activity, adds a new member to the growing list of virus-encoded RNA chaperones, and provides novel knowledge about the virology of EV71

RH20T: A Comprehensive Robotic Dataset for Learning Diverse Skills in One-Shot

A key challenge in robotic manipulation in open domains is how to acquire diverse and generalizable skills for robots. Recent research in one-shot imitation learning has shown promise in transferring trained policies to new tasks based on demonstrations. This feature is attractive for enabling robots to acquire new skills and improving task and motion planning. However, due to limitations in the training dataset, the current focus of the community has mainly been on simple cases, such as push or pick-place tasks, relying solely on visual guidance. In reality, there are many complex skills, some of which may even require both visual and tactile perception to solve. This paper aims to unlock the potential for an agent to generalize to hundreds of real-world skills with multi-modal perception. To achieve this, we have collected a dataset comprising over 110,000 contact-rich robot manipulation sequences across diverse skills, contexts, robots, and camera viewpoints, all collected in the real world. Each sequence in the dataset includes visual, force, audio, and action information. Moreover, we also provide a corresponding human demonstration video and a language description for each robot sequence. We have invested significant efforts in calibrating all the sensors and ensuring a high-quality dataset. The dataset is made publicly available at rh20t.github.ioComment: RSS 2023 workshop on LTAMP. The project page is at rh20t.github.i

Grazing weakens competitive interactions between active methanotrophs and nitrifiers modulating greenhouse-gas emissions in grassland soils

This work was financially supported by Natural Science Foundation of China (41977033, 41907026, and 41721001), Fundamental Research Funds for the Central Universities (2019QNA6011), National Key Basic Research Program of China (2014CB138801), Shandong Provincial Natural Science Foundation (ZR2019BD032), China Postdoctoral Science Foundation (2020T130387 and 2019M652448). CG-R was funded by a Royal Society University Research Fellowship (UF150571). Special thanks to ChunMei Meng, Yu Luo, and Yan Zheng for their assistance in laboratory analyses.Peer reviewedPublisher PD

Repairing Effect of Fucoxanthin on Non-alcoholic Fatty Liver Disease in Mice

Objective: To explore the repairing effect and underlying mechanism of fucoxanthin on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in C57BL/6 mice. Methods: Fifty-two C57BL/6 mice were randomly divided into four groups, including one normal group (n = 14) and three experimental groups (n = 38). The normal group was fed a regular diet, and the experimental groups were fed a HFD. After feeding for eight weeks, two animals were selected from the experimental groups for serum biochemical assays and liver histological observation, and the other 36 were divided into three groups (n = 12 each): model, low-dose and high-dose fucoxanthin, which were then administrated with physiological saline or fucoxanthin by gavage once a day for six weeks. Body mass was recorded weekly, and all mice were killed after fasting for 12 h at the end of the 14th week. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), free fatty acid (FFA), adiponectin, and leptin were measured. In addition, the levels of superoxide dismutase (SOD) activity, glutathione (GSH-Px), malondialdehyde (MDA), catalase (CAT), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in liver homogenate were also determined. Furthermore, hepatic histopathological changes were observed under microscope, and the protein expressions of the adenosine 5’-monophosphate-activated protein kinase (AMPK), nuclear factor erythroid 2-related factor 2 (Nrf2) and toll-like receptors 4 (TLR4) signaling pathways in liver tissues were detected by Western blot. Results: Compared with the model group, the levels of TC, TG, LDL-C, ALT and AST in the fucoxanthin-treated groups were significantly decreased (P < 0.05), Leptin was decreased, while the levels of HDL-C and adiponectin were significantly increased (P < 0.05). Moreover, the levels of GSH-Px, SOD and CAT in the fucoxanthin-treated groups were significantly increased (P < 0.05), leptin was decreased, while the levels of MDA and inflammatory cytokines were significantly decreased (P < 0.05) compared with the model group. The results of hematoxylin-eosin (H&E) staining, oil red O staining, periodic acid-schiff staining (PAS), and transmission electron microscopy (TEM) showed that the histological structure of the liver in the fucoxanthin-treated groups recovered to almost normal. The results of Western blot showed that fucoxanthin treatment upregulated the protein expression of phosphorylated adenosine 5’-monophosphate-activated protein kinase (p-AMPK), peroxisome proliferators-activated receptor α (PPARα), phosphorylated acetyl-CoA carboxylase (p-ACC), and carnitine acyl transferase 1 (CPT-1) in the AMPK signaling pathway, downregulated the expression of sterol regulatory element binding protein-1c (SREBP-1c) and fatty acid synthase (FAS), inhibited the level of Kelch-like epichlorohydrin-associated protein-1 (Keap-1) in the Keap-1/nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway, increased the expression of Nrf2 and its downstream antioxidant proteins heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and glutamate cysteine ligase modifier (GCLM), and downregulated the expression of TLR4, myeloid differentiation factor 88 (MyD88), phosphorylated nuclear factor κB inhibitory protein α (p-IκBα), and phosphorylated nuclear factor κB (p65) (p-NF-κB (p65)) in the TLR4 signaling pathway. Conclusion: Fucoxanthin can repair HFD-induced NAFLD in mice through regulating lipid metabolism, reducing oxidative stress and suppressing inflammation

RETRACTED: Quercetin Inhibits Tumorigenesis of Colorectal Cancer Through Downregulation of hsa_circ_0006990

Quercetin can significantly inhibit the progression of colorectal cancer (CRC). However, its specific mechanism remains largely unclear. In this study, we aimed to explore the correlation among quercetin, tumour-associated macrophages (TAMs) and circular RNAs (circRNAs) in the progression of CRC and to present a novel strategy for the treatment of CRC. In this study, we revealed that quercetin could suppress the autophagy of M2-TAMs and induced their differentiation into M1-TAMs, by which quercetin significantly reversed the inhibition of M2-TAMS on CRC cell apoptosis and the promotion of M2-TAMS on CRC cell proliferation. Moreover, quercetin could promote the expression of downregulated hsa_circ_0006990 in CRC cells co-cultured with M2-TAMs, and the overexpression of hsa_circ_0006990 significantly reversed the anti-tumour effect of quercetin on CRC. Furthermore, we found quercetin can notably suppress the progression of CRC via mediation of the hsa_circ_0006990/miR-132-3p/MUC13 axis. In conclusion, our results suggested that quercetin inhibits the tumorigenesis of CRC via inhibiting the polarisation of M2 macrophages and downregulating hsa_circ_0006990. Our study provides useful insights for those exploring new methods of treating CRC

A general route via formamide condensation to prepare atomically dispersed metal-nitrogen-carbon electrocatalysts for energy technologies

Single-atom electrocatalysts (SAECs) have gained tremendous attention due to their unique active sites and strong metal–substrate interactions. However, the current synthesis of SAECs mostly relies on costly precursors and rigid synthetic conditions and often results in very low content of single-site metal atoms. Herein, we report an efficient synthesis method to prepare metal–nitrogen–carbon SAECs based on formamide condensation and carbonization, featuring a cost-effective general methodology for the mass production of SAECs with high loading of atomically dispersed metal sites. The products with metal inclusion were termed as formamide-converted metal–nitrogen–carbon (shortened as f-MNC) materials. Seven types of single-metallic f-MNC (Fe, Co, Ni, Mn, Zn, Mo and Ir), two bi-metallic (ZnFe and ZnCo) and one tri-metallic (ZnFeCo) SAECs were synthesized to demonstrate the generality of the methodology developed. Remarkably, these f-MNC SAECs can be coated onto various supports with an ultrathin layer as pyrolysis-free electrocatalysts, among which the carbon nanotube-supported f-FeNC and f-NiNC SAECs showed high performance for the O2 reduction reaction (ORR) and the CO2 reduction reaction (CO2RR), respectively. Furthermore, the pyrolysis products of supported f-MNC can still render isolated metallic sites with excellent activity, as exemplified by the bi-metallic f-FeCoNC SAEC, which exhibited outstanding ORR performance in both alkaline and acid electrolytes by delivering ∼70 and ∼20 mV higher half-wave potentials than that of commercial 20 wt% Pt/C, respectively. This work offers a feasible approach to design and manufacture SAECs with tuneable atomic metal components and high density of single-site metal loading, and thus may accelerate the deployment of SAECs for various energy technology applications

Streptococcal Toxic Shock Syndrome Caused by Streptococcus suis Serotype 2

BACKGROUND: Streptococcus suis serotype 2 ( S. suis 2, SS2) is a major zoonotic pathogen that causes only sporadic cases of meningitis and sepsis in humans. Most if not all cases of Streptococcal toxic shock syndrome (STSS) that have been well-documented to date were associated with the non-SS2 group A streptococcus (GAS). However, a recent large-scale outbreak of SS2 in Sichuan Province, China, appeared to be caused by more invasive deep-tissue infection with STSS, characterized by acute high fever, vascular collapse, hypotension, shock, and multiple organ failure. METHODS AND FINDINGS: We investigated this outbreak of SS2 infections in both human and pigs, which took place from July to August, 2005, through clinical observation and laboratory experiments. Clinical and pathological characterization of the human patients revealed the hallmarks of typical STSS, which to date had only been associated with GAS infection. Retrospectively, we found that this outbreak was very similar to an earlier outbreak in Jiangsu Province, China, in 1998. We isolated and analyzed 37 bacterial strains from human specimens and eight from pig specimens of the recent outbreak, as well as three human isolates and two pig isolates from the 1998 outbreak we had kept in our laboratory. The bacterial isolates were examined using light microscopy observation, pig infection experiments, multiplex-PCR assay, as well as restriction fragment length polymorphisms (RFLP) and multiple sequence alignment analyses. Multiple lines of evidence confirmed that highly virulent strains of SS2 were the causative agents of both outbreaks. CONCLUSIONS: We report, to our knowledge for the first time, two outbreaks of STSS caused by SS2, a non-GAS streptococcus. The 2005 outbreak was associated with 38 deaths out of 204 documented human cases; the 1998 outbreak with 14 deaths out of 25 reported human cases. Most of the fatal cases were characterized by STSS; some of them by meningitis or severe septicemia. The molecular mechanisms underlying these human STSS outbreaks in human beings remain unclear and an objective for further study