Variation P-Set and Its Structure

AbstractVariation P-set is put forward from attribute viewpoint, and its structure is given. Variation P-set is composed of variation interior P-set and variation outer P-set. Duality theorems between variation P-set and P-set are proposed. The properties of variation P-set are discussed, and the interior P-theorem, outer P-theorem of variation P-set and discrete interval dynamic generation theorem of the packet degree are proposed. The relations between variation P-set and P-set are analyzed, and the interior P-decomposition theorem and outer P-decomposition theorem of variation P-set are obtained. Variation P-set is a new research direction of P-set

The rice ERF transcription factor OsERF922 negatively regulates resistance to Magnaporthe oryzae and salt tolerance

Rice OsERF922, encoding an APETELA2/ethylene response factor (AP2/ERF) type transcription factor, is rapidly and strongly induced by abscisic acid (ABA) and salt treatments, as well as by both virulent and avirulent pathovars of Magnaporthe oryzae, the causal agent of rice blast disease. OsERF922 is localized to the nucleus, binds specifically to the GCC box sequence, and acts as a transcriptional activator in plant cells. Knockdown of OsERF922 by means of RNAi enhanced resistance against M. oryzae. The elevated disease resistance of the RNAi plants was associated with increased expression of PR, PAL, and the other genes encoding phytoalexin biosynthetic enzymes and without M. oryzae infection. In contrast, OsERF922-overexpressing plants showed reduced expression of these defence-related genes and enhanced susceptibility to M. oryzae. In addition, the OsERF922-overexpressing lines exhibited decreased tolerance to salt stress with an increased Na+/K+ ratio in the shoots. The ABA levels were found increased in the overexpressing lines and decreased in the RNAi plants. Expression of the ABA biosynthesis-related genes, 9-cis-epoxycarotenoid dioxygenase (NCED) 3 and 4, was upregulated in the OsERF922-overexpressing plants, and NCED4 was downregulated in the RNAi lines. These results suggest that OsERF922 is integrated into the cross-talk between biotic and abiotic stress-signalling networks perhaps through modulation of the ABA levels

A Smac-mimetic sensitizes prostate cancer cells to TRAIL-induced apoptosis via modulating both IAPs and NF-kappaB

<p>Abstract</p> <p>Background</p> <p>Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent for human cancer therapy, prostate cancer still remains resistant to TRAIL. Both X-linked inhibitor of apoptosis (XIAP) and nuclear factor-kappaB function as key negative regulators of TRAIL signaling. In this study, we evaluated the effect of SH122, a small molecule mimetic of the second mitochondria-derived activator of caspases (Smac), on TRAIL-induced apoptosis in prostate cancer cells.</p> <p>Methods</p> <p>The potential of Smac-mimetics to bind XIAP or cIAP-1 was examined by pull-down assay. Cytotoxicity of TRAIL and/or Smac-mimetics was determined by a standard cell growth assay. Silencing of XIAP or cIAP-1 was achieved by transient transfection of short hairpin RNA. Apoptosis was detected by Annexin V-PI staining followed by flow cytometry and by Western Blot analysis of caspases, PARP and Bid. NF-kappaB activation was determined by subcellular fractionation, real time RT-PCR and reporter assay.</p> <p>Results</p> <p>SH122, but not its inactive analog, binds to XIAP and cIAP-1. SH122 significantly sensitized prostate cancer cells to TRAIL-mediated cell death. Moreover, SH122 enhanced TRAIL-induced apoptosis via both the death receptor and the mitochondrial pathway. Knockdown of both XIAP and cIAP-1 sensitized cellular response to TRAIL. XIAP-knockdown attenuated sensitivity of SH122 to TRAIL-induced cytotoxicity, confirming that XIAP is an important target for IAP-inhibitor-mediated TRAIL sensitization. SH122 also suppressed TRAIL-induced NF-kappaB activation by preventing cytosolic IkappaB-alpha degradation and RelA nuclear translocation, as well as by suppressing NF-kappaB target gene expression.</p> <p>Conclusion</p> <p>These results demonstrate that SH122 sensitizes human prostate cancer cells to TRAIL-induced apoptosis by mimicking Smac and blocking both IAPs and NF-kappaB. Modulating IAPs may represent a promising approach to overcoming TRAIL-resistance in human prostate cancer with constitutively active NF-kappaB signaling.</p

Multiomics integration reveals the effect of Orexin A on glioblastoma

Objectives: This study involved a multi-omics analysis of glioblastoma (GBM) samples to elaborate the potential mechanism of drug treatment.Methods: The GBM cells treated with or without orexin A were acquired from sequencing analysis. Differentially expressed genes/proteins/metabolites (DEGs/ DEPs/ DEMs) were screened. Next, combination analyses were conducted to investigate the common pathways and correlations between the two groups. Lastly, transcriptome-proteome-metabolome association analysis was carried out to determine the common pathways, and the genes in these pathways were analyzed through Kaplan-Meier (K-M) survival analysis in public databases. Cell and animal experiments were performed to investigate the anti-glioma activity of orexin A.Results: A total of 1,527 DEGs, 52 DEPs, and 153 DEMs were found. Moreover, the combination analyses revealed that 6, 4, and 1 common pathways were present in the transcriptome-proteome, proteome-metabolome, and transcriptome-metabolome, respectively. Certain correlations were observed between the two data sets. Finally, 11 common pathways were discovered in association analysis, and 138 common genes were screened out in these common pathways. Six genes showed significant differences in terms of survival in both TCGA and CGGA. In addition, orexin A inhibited the proliferation, migration, and invasion of glioma in vitro and in vivo.Conclusion: Eleven common KEGG pathways with six common genes were found among different omics participations, revealing the underlying mechanisms in different omics and providing theoretical basis and reference for multi-omics research on drug treatment

Citrus sinensis MYB Transcription Factor CsMYB85 Induce Fruit Juice Sac Lignification Through Interaction With Other CsMYB Transcription Factors

Varieties of Citrus are commercially important fruits that are cultivated worldwide and are valued for being highly nutritious and having an appealing flavor. Lignification of citrus fruit juice sacs is a serious physiological disorder that occurs during postharvest storage, for which the underlying transcriptional regulatory mechanisms remain unclear. In this study, we identified and isolated a candidate MYB transcription factor, CsMYB85, that is involved in the regulation of lignin biosynthesis in Citrus sinensis, which has homologs in Arabidopsis and other plants. We found that during juice sac lignification, CsMYB85 expression levels increase significantly, and therefore, suspected that this gene may control lignin biosynthesis during the lignification process. Our results indicated that CsMYB85 binds the CsMYB330 promoter, regulates its expression, and interacts with CsMYB308 in transgenic yeast and tobacco. A transient expression assay indicated that Cs4CL1 expression levels and lignin content significantly increased in fruit juice sacs overexpressing CsMYB85. At4CL1 expression levels and lignin content were also significantly increased in Arabidopsis overexpressing CsMYB85. We accordingly present convincing evidence for the participation of the CsMYB85 transcription factor in fruit juice sac lignification, and thereby provide new insights into the transcriptional regulation of this process in citrus fruits

Suppressive effect of reactive oxygen species on CD40-induced B cell activation

AbstractReactive oxygen species (ROS) produced by the innate immune system work as effectors to destroy pathogens and to control cellular responses. However, their role in the adaptive immune response remains unclear. Here we studied the effect of exogenous ROS on CD40-induced B cell activation. H2O2 treatment inhibited CD40-induced immunoglobulin production of B cells, DNA binding of NF-κB, IκBα degradation and IKK phosphorylation. On the other hand, H2O2 treatment did not induce obvious B cell death after 30min of stimulation. Although the ligation of anti-CD40 antibody was not disturbed by H2O2, TRAF2 recruitment to CD40 was inhibited. These results suggest that exogenous ROS play a negative role in CD40 signaling during B cell activation

Intelligent tunable CAR-T cell therapy leads the new trend

Adoptive transfer of T cells engineered with chimeric antigen receptor (CAR) has been proved to have robust anti-tumor effects against hematological malignancies. However, problems about safety and efficacy, such as cytokine release syndrome (CRS), T cell exhaustion and antigen escape are still raised when patients are treated with CAR-T cells. Moreover, CAR-T therapy has limited applications in treating solid tumors, owing to inefficient infiltration and poor functional persistence of CAR-T cells and diverse immunosuppression in tumor microenvironment. In order to overcome these limitations and broad its applications, multiple controllable CAR-T technologies were exploited. In this article, we review the designs of intelligent controlled CAR-T technologies and the innovations that they bring about in recent years