Identification of a cellular senescence-related-lncRNA (SRlncRNA) signature to predict the overall survival of glioma patients and the tumor immune microenvironment

Background: Gliomas are brain tumors that arise from glial cells, and they are the most common primary intracranial tumors with a poor prognosis. Cellular senescence plays a critical role in cancer, especially in glioma. In this study, we constructed a senescence-related lncRNA (SRlncRNA) signature to assess the prognosis of glioma.Methods: The Cancer Genome Atlas was used to collect SRlncRNA transcriptome profiles and clinical data about glioma. Patients were randomized to training, testing, and whole cohorts. LASSO and Cox regression analyses were employed to construct the SRlncRNA signature, and Kaplan–Meier (K-M) analysis was performed to determine each cohort’s survival. Receiver operating characteristic (ROC) curves were applied to verify the accuracy of this signature. Gene set enrichment analysis was used to visualize functional enrichment (GSEA). The CIBERSORT algorithm, ESTIMATE and TIMER databases were utilized to evaluate the differences in the infiltration of 22 types of immune cells and their association with the signature. RT–qPCR and IHC were used to identify the consistency of the signature in tumor tissue.Results: An SRlncRNA signature consisting of six long non-coding RNAs (lncRNAs) was constructed, and patients were divided into high-risk and low-risk groups by the median of their riskscore. The KM analysis showed that the high-risk group had worse overall survival, and the ROC curve confirmed that the riskscore had more accurate predictive power. A multivariate Cox analysis and its scatter plot with clinical characteristics confirmed the riskscore as an independent risk factor for overall survival. GSEA showed that the GO and KEGG pathways were mainly enriched in the immune response to tumor cells, p53 signaling pathway, mTOR signaling pathway, and Wnt signaling pathway. Further validation also yielded significant differences in the risk signature in terms of immune cell infiltration, which may be closely related to prognostic differences, and qRT–PCR and IHC confirmed the consistency of the expression differences in the major lncRNAs with those in the prediction model.Conclusion Our findings indicated that the SRlncRNA signature might be used as a predictive biomarker and that there is a link between it and immune infiltration. This discovery is consistent with the present categorization system and may open new avenues for research and personalized therapy

Identification of SNPs and Candidate Genes Associated With Salt Tolerance at the Seedling Stage in Cotton (Gossypium hirsutum L.)

Salt tolerance in cotton is highly imperative for improvement in the response to decreasing farmland and soil salinization. However, little is known about the genetic basis underlying salt tolerance in cotton, especially the seedling stage. In this study, we evaluated two salt-tolerance-related traits of a natural population comprising 713 upland cotton (Gossypium hirsutum L.) accessions worldwide at the seedling stage and performed a genome-wide association study (GWAS) to identify marker-trait associations under salt stress using the Illumina Infinium CottonSNP63K array. A total of 23 single nucleotide polymorphisms (SNPs) that represented seven genomic regions on chromosomes A01, A10, D02, D08, D09, D10, and D11 were significantly associated with the two salt-tolerance-related traits, relative survival rate (RSR) and salt tolerance level (STL). Of these, the two SNPs i46598Gh and i47388Gh on D09 were simultaneously associated with the two traits. Based on all loci, we screened 280 possible candidate genes showing different expression levels under salt stress. Most of these genes were involved in transcription factors, transporters and enzymes and were previously reported as being involved in plant salt tolerance, such as NAC, MYB, NXH, WD40, CDPK, LEA, and CIPK. We further validated six putative candidate genes by qRT-PCR and found a differential expression level between salt-tolerant and salt-sensitive varieties. Our findings provide valuable information for enhancing the understanding of complicated mechanisms of salt tolerance in G. hirsutum seedlings and cotton salt tolerance breeding by molecular marker-assisted selection

Genome sequence of the cultivated cotton <i>Gossypium arboreum</i>

The complex allotetraploid nature of the cotton genome (AADD; 2n = 52) makes genetic, genomic and functional analyses extremely challenging. Here we sequenced and assembled the Gossypium arboreum (AA; 2n = 26) genome, a putative contributor of the A subgenome. A total of 193.6 Gb of clean sequence covering the genome by 112.6-fold was obtained by paired-end sequencing. We further anchored and oriented 90.4% of the assembly on 13 pseudochromosomes and found that 68.5% of the genome is occupied by repetitive DNA sequences. We predicted 41,330 protein-coding genes in G. arboreum. Two whole-genome duplications were shared by G. arboreum and Gossypium raimondii before speciation. Insertions of long terminal repeats in the past 5 million years are responsible for the twofold difference in the sizes of these genomes. Comparative transcriptome studies showed the key role of the nucleotide binding site (NBS)-encoding gene family in resistance to Verticillium dahliae and the involvement of ethylene in the development of cotton fiber cells.Genetics &amp; HereditySCI(E)[email protected]; [email protected]; [email protected]

The Role of MicroRNA in the Regulation of Tumor Epithelial–Mesenchymal Transition

Consistently, the high metastasis of cancer cells is the bottleneck in the process of tumor treatment. In this process of metastasis, a pivotal role is executed by epithelial–mesenchymal transition (EMT). The epithelial-to-mesenchymal transformation was first proposed to occur during embryonic development. Later, its important role in explaining embryonic developmental processes was widely reported. Recently, EMT and its intermediate state were also identified as crucial drivers in tumor progression with the gradual deepening of research. To gain insights into the potential mechanism, increasing attention has been focused on the EMT-related transcription factors. Correspondingly, miRNAs target transcription factors to control the EMT process of tumor cells in different types of cancers, while there are still many exciting and challenging questions about the phenomenon of microRNA regulation of cancer EMT. We describe the relevant mechanisms of miRNAs regulating EMT, and trace the regulatory roles and functions of major EMT-related transcription factors, including Snail, Twist, zinc finger E-box-binding homeobox (ZEB), and other families. In addition, on the basis of the complex regulatory network, we hope that the exploration of the regulatory relationship of non-transcription factors will provide a better understanding of EMT and cancer metastasis. The identification of the mechanism leading to the activation of EMT programs during diverse disease processes also provides a new protocol for the plasticity of distinct cellular phenotypes and possible therapeutic interventions. Here, we summarize the recent progress in this direction, with a promising path for further insight into this fast-moving field

A Robust Flow-Through Platform for Organic Contaminant Removal

© 2020 The Authors Achieving the greatest cleanup efficiency with minimal footprint remains a paramount goal of the water treatment industry. Toxic organic compounds threaten drinking water safety and require effective pretreatment. Hydroxyl radicals produced by the Fenton process (Fe2+/H2O2) destroy organic contaminants based on their strong oxidation potential. An upgraded reaction using solid catalysts, referred to as the Fenton-like process, was recently adopted to avoid the ferric sludge generation during the conventional Fenton process. However, most heterogeneous Fenton-like catalysts operate optimally at pH 3–5 and quite weakly in near-neutral water bodies. Here, we evaluate the feasibility of an electrolytically localized acid compartment (referred to as the Ella process) produced by electrochemical water splitting under flow-through conditions to facilitate the Fenton-like process. The Ella process boosts the activity of an immobilized iron oxychloride catalyst >10-fold, decomposing organic pollutants at a high flow rate. The robust performance in complex water bodies further highlights the promise of this platform

An investigation into random lasing from thin film on a sandpaper substrate

The blender of active material R6G and film forming agent PDMS are spincoated onto a sandpaper substrate to fabricate the random laser of thin layer. The sandpaper provides support for the random laser and the sand particles on the sandpaper substrate provide the scattering mechanism of random lasing output. The random lasing emission centres at 560 nm, with a threshold of about 13 mJ/cm2. This design provides a new and cheap method to fabricate random lasers

Distinct Roles of Nrf1 and Nrf2 in Monitoring the Reductive Stress Response to Dithiothreitol (DTT)

Transcription factor Nrf2 (nuclear factor, erythroid 2-like 2, encoded by Nfe2l2) has been accepted as a key player in redox regulatory responses to oxidative or reductive stresses. However, relatively little is known about the potential role of Nrf1 (nuclear factor, erythroid 2-like 1, encoded by Nfe2l1) in the redox responses, particularly to reductive stress, although this &lsquo;fossil-like&rsquo; factor is indispensable for cell homeostasis and organ integrity during the life process. Herein, we examine distinct roles of Nrf1 and Nrf2 in monitoring the defense response to 1,4&ndash;dithiothreitol (DTT, serving as a reductive stressor), concomitantly with unfolded protein response being induced by this chemical (also defined as an endoplasmic reticulum stressor). The results revealed that intracellular reactive oxygen species (ROS) were modestly increased in DTT-treated wild-type (WT) and Nrf1&alpha;&minus;/&minus; cell lines, but almost unaltered in Nrf2&minus;/&minus;&Delta;TA or caNrf2&Delta;N cell lines (with a genetic loss of transactivation or N-terminal Keap1-binding domains, respectively). This chemical treatment also enabled the rate of oxidized to reduced glutathione (i.e., GSSG to GSH) to be amplified in WT and Nrf2&minus;/&minus;&Delta;TA cells, but diminished in Nrf1&alpha;&minus;/&minus; cells, along with no changes in caNrf2&Delta;N cells. Consequently, Nrf1&alpha;&minus;/&minus;, but not Nrf2&minus;/&minus;&Delta;TA or caNrf2&Delta;N, cell viability was reinforced by DTT against its cytotoxicity, as accompanied by decreased apoptosis. Further experiments unraveled that Nrf1 and Nrf2 differentially, and also synergistically, regulated DTT-inducible expression of critical genes for defending against redox stress and endoplasmic reticulum stress. In addition, we also identified that Cys342 and Cys640 of Nrf1 (as redox-sensing sites within its N-glycodomain and DNA-binding domain, respectively) are required for its protein stability and transcription activity

Nrf1 is not a direct target gene of SREBP1, albeit both are integrated into the rapamycin-responsive regulatory network in human hepatoma cells.

The essential role of protein degradation by ubiquitin-proteasome system is exerted primarily for maintaining cellular protein homeostasis. The transcriptional activation of proteasomal genes by mTORC1 signaling depends on Nrf1, but whether this process is directly via SREBP1 remains elusive. In this study, our experiment evidence revealed that Nrf1 is not a direct target of SREBP1, although both are involved in the rapamycin-responsive regulatory networks. Closely scrutinizing two distinct transcriptomic datasets unraveled no significant changes in transcriptional expression of Nrf1 and almost all proteasomal subunits in either siSREBP2-silencing cells or SREBP1-∕-MEFs, when compared to equivalent controls. However, distinct upstream signaling to Nrf1 dislocation by p97 and its processing by DDI1/2, along with downstream proteasomal expression, may be monitored by mTOR signaling, to various certain extents, depending on distinct experimental settings in different types of cells. Our further evidence has been obtained from DDI1-∕-(DDI2insC) cells, demonstrating that putative effects of mTOR on the rapamycin-responsive signaling to Nrf1 and proteasomes may also be executed partially through a DDI1/2-independent mechanism, albeit the detailed regulatory events remain to be determined

Peg-Enhanced Behavioral Recovery After Sciatic Nerve Transection and Either Suturing Or Sleeve Conduit Deployment in Rats

Polyethylene glycol (PEG) has previously been reported to improve outcomes of peripheral nerve microsuturing. However, recent studies have challenged this finding. Given its clinical importance, we investigated the potential of PEG as a facilitator of peripheral nerve restoration. The sciatic nerve of 144 rats was transected and submitted either to simple suturing (Group A), PEG-enhanced suturing (Group B), and insertion in an arterial sleeve conduit without PEG (Group C), or with PEG (Group D) in equal numbers. Behavioral recovery was assessed with the sciatic function index (SFI). Nerve impulse conduction was assessed with compound muscle action potentials (CMAPs). Histology comprised standard hematoxylin/eosin staining, electron microscopy and glial cell line-derived neurotrophic factor (GDNF) immunohistochemistry. Expression of GDNF was also assessed with western blotting. Results were evaluated at weeks 1, 4, and 8. PEG treatment significantly improved behavioral recovery and morphology of nerve restoration, particularly in the sleeve conduit group, relative to that of controls. In conclusion, PEG may improve outcomes of peripheral nerve reconstruction