SteE enhances the colonization of Salmonella Pullorum in chickens

Salmonella pullorum (S. pullorum) is the causative agent of pullorum disease and results in severe economic losses in poultry, and can long-term survival by colonizing host organs. steE is an effector protein secreted by Salmonella pathogenicity island 2. It is not clear in vivo for the colonization of Salmonella. To investigate the role of steE on the colonization of S. Pullorum in the principal organs of chicken, we used S. pullorum and S. pullorum ΔsteE strains immunized chickens, respectively. The results of the virulence assay showed that the LD50 of S. pullorum ΔsteE was 22.8 times higher than that of S. pullorum in chickens. The colonization experiment of bacteria showed that the overall change trend of the number of S. pullorum and S. pullorum ΔsteE strains were similar in chicken liver, spleen, heart, bursa, and cecum, which increased first and then decreased. However, the deletion of steE caused significantly reduced colonization, pathological change, and virulence of S. pullorum in a chicken infection model. Our findings provide exciting insights into the pathogenic mechanism and live attenuated vaccine associated with steE in S. pullorum

Pyroptosis: a new insight into intestinal inflammation and cancer

Pyroptosis is an innate immune response triggered by the activation of inflammasomes by various influencing factors, characterized by cell destruction. It impacts the immune system and cancer immunotherapy. In recent years, the roles of pyroptosis and inflammasomes in intestinal inflammation and cancer have been continuously confirmed. This article reviews the latest progress in pyroptosis mechanisms, new discoveries of inflammasomes, mutual regulation between inflammasomes, and their applications in intestinal diseases. Additionally, potential synergistic treatment mechanisms of intestinal diseases with pyroptosis are summarized, and challenges and future directions are discussed, providing new ideas for pyroptosis therapy

Novel biomarkers predict prognosis and drug-induced neuroendocrine differentiation in patients with prostate cancer

BackgroundA huge focus is being placed on the development of novel signatures in the form of new combinatorial regimens to distinguish the neuroendocrine (NE) characteristics from castration resistant prostate cancer (CRPC) timely and accurately, as well as predict the disease-free survival (DFS) and progression-free survival (PFS) of prostate cancer (PCa) patients.MethodsSingle cell data of 4 normal samples, 3 CRPC samples and 3 CRPC-NE samples were obtained from GEO database, and CellChatDB was used for potential intercellular communication, Secondly, using the “limma” package (v3.52.0), we obtained the differential expressed genes between CRPC and CRPC-NE both in single-cell RNA seq and bulk RNA seq samples, and discovered 12 differential genes characterized by CRPC-NE. Then, on the one hand, the diagnosis model of CRPC-NE is developed by random forest algorithm and artificial neural network (ANN) through Cbioportal database; On the other hand, using the data in Cbioportal and GEO database, the DFS and PFS prognostic model of PCa was established and verified through univariate Cox analysis, least absolute shrinkage and selection operator (Lasso) regression and multivariate Cox regression in R software. Finally, somatic mutation and immune infiltration were also discussed.ResultsOur research shows that there exists specific intercellular communication in classified clusters. Secondly, a CRPC-NE diagnostic model of six genes (HMGN2, MLLT11, SOX4, PCSK1N, RGS16 and PTMA) has been established and verified, the area under the ROC curve (AUC) is as high as 0.952 (95% CI: 0.882−0.994). The mutation landscape shows that these six genes are rarely mutated in the CRPC and NEPC samples. In addition, NE-DFS signature (STMN1 and PCSK1N) and NE-PFS signature (STMN1, UBE2S and HMGN2) are good predictors of DFS and PFS in PCa patients and better than other clinical features. Lastly, the infiltration levels of plasma cells, T cells CD4 naive, Eosinophils and Monocytes were significantly different between the CRPC and NEPC groups.ConclusionsThis study revealed the heterogeneity between CRPC and CRPC-NE from different perspectives, and developed a reliable diagnostic model of CRPC-NE and robust prognostic models for PCa

Inhibition of Aflatoxin Synthesis in Aspergillus flavus by Three Structurally Modified Lentinans

The chemical properties of β-glucans leading to their inhibition on aflatoxin (AF) production by Aspergillus flavus remain unclear. In this study, structurally modified lentinan derivatives were prepared by carboxymethylation, sulfation, and phosphorylation to explore their inhibition activity to AF synthesis. The results demonstrated that inhibitory activity of lentinan decreased at higher or lower concentrations than 200 μg/mL. Compared with lentinan, the sulphated derivatives only performed a reduced optimal inhibition rate at a higher concentration. The phosphorylated derivatives achieved complete inhibition of AF production at 50 μg/mL, but the inhibitory activity was attenuated with an increase of concentration. The minimum concentration of carboxymethylated derivatives to completely inhibit AF synthesis was the same as that of the original lentinan, whereas their inhibition activity was not reduced at the increasing concentration. RT-PCR analyses were conducted to understand the effects of lentinan and its carboxymethylated derivatives on the transcription of certain genes associated with AF biosynthesis. The results showed that lentinan delayed the transcription of aflQ, whereas its carboxymethylated derivatives promoted the transcriptions of all the tested genes. Our results revealed that some chemical group features apart from the β-bond could play the vital role in the prevention of AF formation by polysaccharide, and highlighted the structural modifications which could promote its practicability in the control of aflatoxin contamination

Molecular cloning and characterization of a class II ADP ribosylation factor from the shrimp Marsupenaeus japonicus

Natural Science Foundation of China [30830084]; National Basic Research Program of China [2006CB101804]In shrimp, small GTPases in the Ras superfamily can regulate hemolytic phagocytosis against WSSV infection. However, the ADP ribosylation factors (Arfs), also belonging to the regulatory GTP-bincling proteins and playing a central role in membrane trafficking, have not been reported yet in shrimp and their relationship with WSSV infection is completely unknown to date. Here, a novel class II Arf (designated as MjArf4) was cloned and characterized from the shrimp Marsupenaeus joponicus. Like other Arfs, MjArf4 contains an N-terminal myristoylated site, a p loop, switch regions, as well as an interswitch region. In High Five cells, when MjArf4 was in its GDP-bound form, it dispersed into the whole cell, whereas in the GTP-bound form it promoted formation of a punctuate Golgi-like structure, indicating that the MjArf4 distribution was dependent on its GDP/GTP binding. After challenge with WSSV, the mRNA level of MjArf4 was up-regulated significantly as WSSV propagated. Thus, a member of the Arf family was characterized for the first time in shrimp and found to be involved in WSSV infection. (C) 2009 Elsevier Ltd. All rights reserved

Characterization of two novel ADP ribosylation factors from the shrimp Marsupenaeus japonicus

National 501 Natural Science Foundation of China [30830084]; National Basic Science Research Program of China [2006CB101804]; Earmarked fund for Modern Agro-industry Technology Research SystemADP-ribosylation factors (Arfs) that play an essential role in intracellular trafficking and organelle structure are small GTP-binding proteins, which have been identified recently to be involved in virus infection. However, little is known about the Arfs and their relationships with viral infection in the economically important crustaceans to date. In the present study, two novel members of the Arf family, designated as MjArf1 and MjArfn respectively, were cloned from the shrimp Marsupenaeus japonicus. Sequence and phylogenetic analysis showed that MjArf1 belongs to Class I Arf, which has very high homology in sequence to the known Arf 79F of insects and Arf1 of other animals (96-99%), whereas MjArfn is an unidentified Arf, which has only 62-66% identity to other known Arfs. In High Five cells, the distribution of MjArf1 was dependent on its GDP/GTP binding state but the distribution of MjArfn was not affected by that. Both Arfs were ubiquitously expressed in examined tissues. Further investigation with real-time quantitative PCR revealed that MjArf1 and MjArfn were significantly up-regulated after WSSV challenge. In virus-resistant shrimps, however, no distinct fluctuation of MjArf1 expression was found and MjArfn was even found to be notably repressed. These results suggested that MjArf1 and MjArfn might be involved in the shrimp innate immune response in WSSV infection and MjArfn might play a role in WSSV invasion. These studies may contribute to a better understanding of host defense and/or virus invasion interaction and for the control of marine crustacean diseases. (C) 2010 Elsevier Ltd. All rights reserved

Transcription profiles of the responses of chicken bursae of Fabricius to IBDV in different timing phases

Abstract Background Infectious bursal disease virus (IBDV) infection causes immunosuppression in chickens and increases their susceptibility to secondary infections. To explore the interaction between host and IBDV, RNA-Seq was applied to analyse the transcriptional profiles of the responses of chickens’ bursas of Fabricius in the early stage of IBDV infection. Results The results displayed that a total of 15546 genes were identified in the chicken bursa libraries. Among the annotated genes, there were 2006 and 4668 differentially expressed genes in the infection group compared with the mock group on day 1 and day 3 post inoculation (1 and 3 dpi), respectively. Moreover, there were 676 common up-regulated and 83 common down-regulated genes in the bursae taken from the chickens infected with IBDV on both 1 and 3 dpi. Meanwhile, there were also some characteristic differentially expressed genes on 1 and 3 dpi. On day 1 after inoculation with IBDV, host responses mainly displayed immune response processes, while metabolic pathways played an important role on day three post infection. Six genes were confirmed by quantitative reverse transcription-PCR. Conclusions In conclusion, the differential gene expression profile demonstrated with RNA-Seq might offer a better understanding of the molecular interactions between host and IBDV during the early stage of infection

Betaine Alleviates LPS-Induced Chicken Skeletal Muscle Inflammation with the Epigenetic Modulation of the TLR4 Gene

Betaine was found to alleviate inflammation in different studies. Here, newly hatched broilers were randomly divided into control and betaine consumptive groups, who had access to normal drinking water and water with betaine at a dose of 1000 mg/L, respectively. At the age of two weeks, the boilers were intraperitoneally treated with LPS. The protective effects of betaine against LPS-induced skeletal muscle inflammation were studied. Betaine attenuated the LPS-induced overexpression of IL-6 significantly in the leg muscle. Furthermore, LPS lowered the expression of TLR4 and TLR2 but increased the expression of MyD88. Betaine eliminated the effect of LPS on the expression of TLR4 but not TLR2 and MyD88. LPS also increased the expression of Tet methylcytosine dioxygenase 2 (Tet2), and this effect was also eliminated by betaine consumption. MeDIP-qPCR analysis showed that the methylation level in the promoter region of IL-6 was decreased by LPS treatment, whilst betaine cannot prevent this effect. On the contrary, LPS significantly increase the methylation level in the promoter region of TLR4, which was decreased by the consumption of betaine. Our findings suggest that betaine can alleviate LPS-induced muscle inflammation in chicken, and the regulation of aberrant DNA methylation might be a possible mechanism

Stretchable, Ultratough, and Intrinsically Self-Extinguishing Elastomers with Desirable Recyclability

Advanced elastomers are increasingly used in emerging areas, for example, flexible electronics and devices, and these real-world applications often require elastomers to be stretchable, tough and fire safe. However, to date there are few successes in achieving such a performance portfolio due to their different governing mechanisms. Herein, a stretchable, supertough, and self-extinguishing polyurethane elastomers by introducing dynamic π–π stacking motifs and phosphorus-containing moieties are reported. The resultant elastomer shows a large break strain of ≈2260% and a record-high toughness (ca. 460 MJ m−3), which arises from its dynamic microphase-separated microstructure resulting in increased entropic elasticity, and strain-hardening at large strains. The elastomer also exhibits a self-extinguishing ability thanks to the presence of both phosphorus-containing units and π–π stacking interactions. Its promising applications as a reliable yet recyclable substrate for strain sensors are demonstrated. The work will help to expedite next-generation sustainable advanced elastomers for flexible electronics and devices applications.</p