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Colon adenocarcinoma (COAD) is one of the tumors with the highest mortality rates. It is of the utmost significance to make an accurate prognostic assessment and to tailor one’s treatment to the specific needs of the patient. Multiple lines of evidence point to the possibility that genetic variables and clinicopathological traits are connected to the onset and development of cancer. In the past, a number of studies have revealed that gamma-aminobutyric acid type A receptor subunit delta (GABRD) plays a role in the advancement of a number of different cancers. However, its function in COAD was rarely reported. In this study, we analyzed TCGA datasets and identified 29 survival-related differentially expressed genes (DEGs) in COAD patients. In particular, GABRD expression was noticeably elevated in COAD specimens. There was a correlation between high GABRD expression and an advanced clinical stage. According to the results of the survival tests, patients whose GABRD expression was high had a lower overall survival time and progression-free survival time than those whose GABRD expression was low. GABRD expression was found to be an independent predictive predictor for overall survival, as determined by multivariate COX regression analysis. Additionally, the predictive nomogram model can accurately predict the fate of individuals with COAD. In addition, we observed that GABRD expressions were positively associated with the expression of T cells regulatory (Tregs), macrophages M0, while negatively associated with the expression of T cells CD8, T cells follicular helper, macrophages M1, dendritic cells activated, eosinophils, and T cells CD4 memory activated. The IC50 of BI-2536, bleomycin, embelin, FR-180204, GW843682X, LY317615, NSC-207895, rTRAIL, and VX-11e was higher in the GABRD high-expression group. In conclusion, we have shown evidence that GABRD is a novel biomarker that is connected with immune cell infiltration in COAD and may be utilized to predict the prognosis of COAD patients.

Background In the literature, filum terminale arteriovenous shunts (FTAVSs) always feature a single shunt point. Nidus-type FTAVSs have rarely been reported, and the best treatment strategy is unclear. This is a report of 1 exceptional case of a nidus-type FTAVS and surgical treatment of the lesion. Case description The patient suffered from cauda equina syndrome for 9 months. Magnetic resonance imaging and spinal angiography revealed a nidus-type FTAVF at the L2 level. Surgical resection was performed in the hybrid operating room, and the nidus was completely resected with the assistance of intraoperative methylene blue angiography and neurophysiological monitoring. The postoperative neurological function was stable. Conclusions A nidus-type AVS could originate from the FT, and in such cases, complete surgical resection with intraoperative neurophysiological monitoring in a hybrid operating room should be suggested.

Several locations across the United States in non-compliance with the national standard for ground-level ozone (O

The synthesis of high value-added organic carboxylic acids, especially chiral carboxylic acids, from the electrochemical fixation of CO2 with organic molecules under mild conditions is very important and challenging.

4,4-Bis(2-ethylhexyl)-4H-silolo[3,2-b:4,5-b′]dithiophene was employed as a donor to construct a D–A polymer photocatalyst, which delivers a photocatalytic hydrogen evolution rate of 72.20 mmol h−1 g−1 under full spectrum light with a Pt co-catalyst.

In the past few years, cloud edge system from conception to gradually improve, develop to today has become a mature side of cloud model. Compared with simple cloud computing, cloud edge system has lower network latency and is suitable for application scenarios with higher real-time requirements. Although it can make up for some shortcomings of cloud computing, it also faces many problems in practical application, how to realize the safe transmission of information in the open network environment is one of the difficulties. Since the data transmission process between the edge and the cloud exists in the form of plaintext transmission, this allows attackers to easily disrupt normal data interactions. It is an important research point to ensure the stable operation of the cloud edge system while maximizing the security of communication. To this end, the following work has been done in the direction of secure data transmission in this paper：1. Analyzed the potential risks of the cloud edge system communication network from the per-spective of data source security and data transmission security. 2. Summarizes the requirements and limitations of secure communication, introduces a light-weight SM9 encryption algorithm with low implementation cost and low resource consumption. And compared with other encryption algorithms. 3. Provide algorithmic foundation for establish a framework for secure transmission of light-weight data and achieve data confidentiality protection. Provides a viable reference for secure data transmission in the cloud edge system. &nbsp

Introduction: Functional disorder of the placenta is the principal cause of fetal growth restriction (FGR), usually cured with suitable clinical treatment and good nursing. However, some FGR mothers still give birth to small for gestational age (SGA) babies after treatment. The ineffectiveness of treatment in such a group of patients confused physicians of obstetrics and gynecology.Methods: In this study, we performed a microRNA-messenger RNA integrative analysis of gene expression profiles obtained from Gene Expression Omnibus. Differentially expressed genes were screened and checked using quantitative polymerase chain reaction. Target genes of significantly changed microRNA were screened and enriched for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Function of the obtained microRNA-messenger RNA was evaluated using HTR-8/SVneo trophoblast cells, human umbilical vein endothelial cells, and heterozygote male mice.Result: MiR-155-5p was upregulated (p = 0.001, fold-change = 2.275) in fetal-side placentals. Among the hub genes identified as key targets for miR-155-5p in fetal reprogramming, Smad2 was downregulated (p = 0.002, fold change = 0.426) and negatively correlated with miR-155-5p expression levels (r = −0.471, p < 1.0 E – 04) in fetal-side placental tissues. The miR-155-5p mimic blocks Smad2 expression and suppresses villous trophoblast cell and endothelial cell function (proliferation, migration, and invasion), indicating a close relationship with placental development. Luciferase assays further confirmed the targeting of miR-155-5p to Smad2. Furthermore, Smad2+/− heterozygote male mice were born small with low body weight (p = 0.0281) and fat composition (p = 0.013) in the fourth week post-natal.Discussion: We provide the first evidence of the role of the Smad2/miR-155-5p axis in the placental pathologies of FGR. Our findings elucidate the pathogenesis of FGR and provide new therapeutic targets.

Background The failure of novel therapies effective in preclinical animal models largely reflects the fact that current models do not really mimic the pathological/therapeutic features of glioblastoma (GBM), in which the most effective temozolomide chemoradiotherapy (RT/TMZ) regimen can only slightly extend survival. How to improve RT/TMZ efficacy remains a major challenge in clinic. Methods Syngeneic G422TN-GBM model mice were subject to RT/TMZ, surgery, piperlongumine (PL), αPD1, glutathione. Metabolomics or transcriptomics data from G422TN-GBM and human GBM were used for gene enrichment analysis and estimation of ROS generation/scavenging balance, oxidative stress damage, inflammation and immune cell infiltration. Overall survival, bioluminescent imaging, immunohistochemistry, and immunofluorescence staining were used to examine therapeutic efficacy and mechanisms of action. Results Here we identified that glutathione metabolism was most significantly altered in metabolomics analysis upon RT/TMZ therapies in a truly refractory and reliable mouse triple-negative GBM (G422TN) preclinical model. Consistently, ROS generators/scavengers were highly dysregulated in both G422TN-tumor and human GBM. The ROS-inducer PL synergized surgery/TMZ, surgery/RT/TMZ or RT/TMZ to achieve long-term survival (LTS) in G422TN-mice, but only one LTS-mouse from RT/TMZ/PL therapy passed the rechallenging phase (immune cure). Furthermore, the immunotherapy of RT/TMZ/PL plus anti-PD-1 antibody (αPD1) doubled LTS (50%) and immune-cured (25%) mice. Glutathione completely abolished PL-synergistic effects. Mechanistically, ROS reduction was associated with RT/TMZ-resistance. PL restored ROS level (mainly via reversing Duox2/Gpx2), activated oxidative stress/inflammation/immune responses signature genes, reduced cancer cell proliferation/invasion, increased apoptosis and CD3+/CD4+/CD8+ T-lymphocytes in G422TN-tumor on the basis of RT/TMZ regimen. Conclusion Our findings demonstrate that PL reverses RT/TMZ-reduced ROS and synergistically resets tumor microenvironment to cure GBM. RT/TMZ/PL or RT/TMZ/PL/αPD1 exacts effective immune cure in refractory GBM, deserving a priority for clinical trials.

Temporally heterogeneous environments is hypothesized to correlate with greater plasticity of plants, which has rarely been supported by direct evidence. To address this issue, we subjected three species from different ranges of habitats to a first round of alternating full light and heavy shading (temporally heterogeneous light experience), constant moderate shading and full light conditions (temporally homogeneous light experiences, control) and a second round of light-gradient treatments. We measured plant performance in a series of morphological, biomass, physiological and biochemical traits at the end of each round. Compared to constant full light experience, temporally heterogeneous light conditions induced immediate active biochemical responses (in the first round) with improved late growth in biomass (during the second round); constant moderate shading experience increased photosynthetic physiological and biomass performances of plants in early response, and decreased their late growth in biomass. The karst endemic species of Kmeria septentrionalis showed greater improvement in late growth of biomass and lower decrease in biochemical performance, due to early heterogeneous experience, compared to the non-karst species of Lithocarpus glaber and the karst adaptable species of Celtis sinensis. Results suggested plants will prefer to produce morphological and physiological responses that are less reversible and more costly in the face of more reliable environmental cues at early stage in spite of decreased future growth potential, but to produce immediate biochemical responses for higher late growth potential when early environmental cues are less reliable, to avoid the loss of high costs and low profits. Typical karst species should be more able to benefit from early temporally heterogeneous experience, due to long-term adaptation to karst habitats of high environmental heterogeneity and low resource availability.

Accurate timely estimation of emissions of nitrogen oxides (NO

The binding properties of single noble metal atoms (Pd, Pt and Ir) anchored Janus MoSSe monolayers (MLs), the catalytic activity of Pd- and Pt-MoSSe in oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) as well as the adsorption behaviors of Ir-MoSSe for harmful NO, CO and NH

Background Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system, ranking third for morbidity and mortality worldwide. At present, no effective control method is available for this cancer type. In tumor cells, especially iron metabolization, is necessary for its growth and proliferation. High levels of iron are an important feature to maintain tumor growth; however, the overall mechanism remains unclear. Methods We used western blotting, immunohistochemistry (IHC) and real-time quantitative PCR to analyze the expression of IGF2BP2 in cell lines and tissues. Further, RNA-sequencing, RNA immunoprecipitation and methylated RNA immunoprecipitation experiments explored the specific binding of target genes. Moreover, the RNA stability assay was performed to determine the half-life of genes downstream of IGF2BP2. In addition, the Cell Counting Kit-8, colony formation assay, 5-ethynyl-2’-deoxyuridine assay and flow cytometry were used to evaluate the effects of IGF2BP2 on proliferation and iron metabolism. Lastly, the role of IGF2BP2 in promoting CRC growth was demonstrated in animal models. Results We observed that IGF2BP2 is associated with iron homeostasis and that TFRC is a downstream target of IGF2BP2. Further, overexpression of TFRC can rescue the growth of IGF2BP2-knockdown CRC cells. Mechanistically, we determined that IGF2BP2 regulates TFRC methylation via METTL4, thereby regulating iron metabolism and promoting CRC growth. Furthermore, using animal models, we observed that IGF2BP2 promotes CRC growth. Conclusion IGF2BP2 regulates TFRC mRNA methylation via METTL4, thereby regulating iron metabolism and promoting CRC growth. Our study highlights the key roles of IGF2BP2 in CRC carcinogenesis and the iron transport pathways.

SALT OVERLY SENSITIVE1 (SOS1) is a key component of plant salt tolerance. However, how SOS1 transcription is dynamically regulated in plant response to different salinity conditions remains elusive. Here, we report that C-type Cyclin1;1 (CycC1;1) negatively regulates salt tolerance by interfering with WRKY75-mediated transcriptional activation of SOS1 in Arabidopsis (Arabidopsis thaliana). Disruption of CycC1;1 promotes SOS1 expression and salt tolerance in Arabidopsis because CycC1;1 interferes with RNA polymerase II recruitment by occupying the SOS1 promoter. Enhanced salt tolerance of the cycc1;1 mutant was completely compromised by an SOS1 mutation. Moreover, CycC1;1 physically interacts with the transcription factor WRKY75, which can bind to the SOS1 promoter and activate SOS1 expression. In contrast to the cycc1;1 mutant, the wrky75 mutant has attenuated SOS1 expression and salt tolerance, whereas overexpression of SOS1 rescues the salt sensitivity of wrky75. Intriguingly, CycC1;1 inhibits WRKY75-mediated transcriptional activation of SOS1 via their interaction. Thus, increased SOS1 expression and salt tolerance in cycc1;1 were abolished by WRKY75 mutation. Our findings demonstrate that CycC1;1 forms a complex with WRKY75 to inactivate SOS1 transcription under low salinity conditions. By contrast, under high salinity conditions, SOS1 transcription and plant salt tolerance are activated at least partially by increased WRKY75 expression but decreased CycC1;1 expression.

The effect of miR-644a on cell growth, migration and invasion of KYSE-410 cell line in vitro. A and B, down-regulation of miR-644a significantly promoted cell growth (A) and colony formation (B) compared with that of control cells. C, the wound healing rate in anti-miR-644a-transfected cells was significantly increased. D, the number of invaded cell in anti-miR-644a-transfected group was significantly increased compared to the control group. **P

Shortening of the 3′ untranslated regions (3′UTR) of mRNA is an important mechanism for oncogene activation. However, 3′UTR alteration events, their pathologic functions, and underlying mechanisms in human urothelial carcinoma of the bladder (UCB) are not clear. Here, we combine RNA sequencing, bioinformatics, and clinical studies in two independent cohorts of patients with UCB to identify a novel RAC1 shorter 3′UTR isoform that is frequently expressed in UCB and is critical in the tumorigenesis and acquisition of a poor prognostic phenotype in patients. Short 3′UTR isoform of RAC1 substantially upregulated RAC1 expression by escaping from miRNA-targeted repression and played an essential oncogenic role in UCB pathogenesis. An important cleavage/polyadenylation factor, cleavage stimulation factor 2 (CSTF2), induced 3′UTR shortening of RAC1 in UCB by mediating slow transcriptional elongation at RAC1. Cotranscriptional recruitment of CSTF2 on the GUAAU motif at proximal polyadenylation site of RAC1 attenuated the recruitment of two transcription factors AFF1 and AFF4, causing the defects in elongation. CSTF2 regulated the tumorigenic functions of the shorter RAC1 isoform in UCB cells, enhancing cell proliferation, migration, and invasion. The combination of high expression of CSTF2 and high usage of RAC1 short-3′UTR isoform may be used as a powerful biomarker to predict poor prognosis in UCB. Our findings also suggest a CSTF2-regulated RAC1-3′UTR shortening program as an exploitable therapeutic strategy for patients with UCB.Significance: These findings demonstrate that the short isoform of RAC1 is critical in UCB tumorigenesis and may have implications for developing new therapeutic strategies to treat this disease. Cancer Res; 78(20); 5848–62. ©2018 AACR.

Figure S2. PITX2 is a direct target of miR-644a in ESCC. A, miR-644a and its putative binding sequence in the 3'-UTR of PITX2. The mutant miR-644a-binding site was generated in the complementary site for the seed region of miR-644a (wt: wild type; mt: mutant type). B, miR-644a significantly suppressed the luciferase activity that carried wt but not mt 3'-UTR of PITX2. C and D, up-regulation of miR-644a significantly reduced PITX2 protein (C) and mRNA levels (D) of KYSE-140 and Eca-109 cells. E, PITX2 expression in subcutaneous implantation models of KYSE-140 and Eca-109 cells detected by IHC staining. **P

Inhibitory effects of miR-644a on the protein expression of PITX2-AKT- GSK-3β-β-catenin axis in vivo. Upper panel, representative images showing the protein expressions of PITX2, P-AKT, P-GSK-3β and active β-catenin examined by IHC in xenograf tissues from miR-644a-overexpressing ESCC and control cells. Lower panel, the IHC scores of PITX2, P-AKT, P-GSK-3β and active β-catenin were significantly lower in xenograft tissues from miR-644a-overexpressing ESCC cells compared to that of control ESCC cells. **P

Purpose:We previously reported the oncogenic role of paired-like homeodomain 2 (PITX2) in esophageal squamous cell carcinoma (ESCC). In this study, we aimed to identify the miRNA regulators of PITX2 and the mechanism underlying the pathogenesis of ESCC.Experimental Design:Using miRNA profiling and bioinformatics analyses, we identified miR-644a as a negative mediator of PITX2 in ESCC. A series of in vivo and in vitro assays were performed to confirm the effect of miR-644a on PITX2-mediated ESCC malignancy.Results:ESCC cells and tissues expressed less miR-644a than normal epithelial controls. In patient samples, lower expression of miR-644a in ESCC tissues was significantly correlated with tumor recurrence and/or metastasis, such that miR-644a, PITX2, and the combination of the two were independent prognostic indicators for ESCC patient's survival (P < 0.05). Gain- and loss-of-function studies demonstrated that miR-644a inhibited ESCC cell growth, migration, and invasion in vitro and suppressed tumor growth and metastasis in vivo. In addition, miR-644a dramatically suppressed self-renewal and stem cell–like traits in ESCC cells. Furthermore, the effect of upregulation of miR-644a was similar to that of PITX2 knockdown in ESCC cells. Mechanistic studies revealed that miR-644a attenuates ESCC cells' malignancy and stem cell–associated phenotype, at least partially, by inactivation of the Akt/GSK-3β/β-catenin signaling pathway through PITX2. Furthermore, promoter hypermethylation caused downregulation of miR-644a in ESCC.Conclusions:Downregulation of miR-644a plays an important role in promoting both aggressiveness and stem-like traits of ESCC cells, suggesting that miR-644a may be useful as a novel prognostic biomarker or therapeutic target for the disease. Clin Cancer Res; 23(1); 298–310. ©2016 AACR.

MiR-644a inhibits the stemness of Eca-109 cells by regulating PITX2 expression. A-D, enforced overexpression of miR-644a in Eca-109 cells substantially down-regulated the levels of stemness-associated genes (Nanog, Oct-4, Bmi-1, Notch-1 and Smo), multiple drug-resistance transporter genes (ABCC2, ABCG2) and surface antigens associated with cancer stem cells (CD24, CD44, CD133, CD105, and CD166) (A), reduced phere-forming ability (B) and proportion of side-population cells (C), and also largely increased chemosensitivity to cisplatin or radiosensitivity to IR (D). Restoration of PITX2 in miR-644a-overexpressing Eca-109 cells largely rescued the cells' stemness, while knockdown of PITX2 by shPITX2 decreased Eca-109 cells' stemness (A-D). E, tumor formation in nude mice shows reduced tumorigenicity in 3 groups of miR-644a-overexpressing Eca-109 cells indicated, as compared to that in matched control groups. *P

Correlation between the expressions of miR-644a and pluripotency-associated factors in 20 fresh ESCC tissues. A, real-time PCR analysis of the mRNA expression of pluripotency-associated factors, including ABCG2, SOX2, OCT4, NANOG, BMI1, and CD44 in 20 ESCC samples. B, the levels of miR-644a were negatively correlated with the expression levels of pluripotency-associated factors in 20 ESCC tissues. **P

Supplementary Figure S1. Identification of 3'UTR shortening of RALA and RAC1 from UCB, colorectal carcinoma, hepatocellular carcinoma and non-small cell lung cancer samples. Supplementary Figure S2. RAC1 with short 3'UTR promotes tumorigenesis and produces more protein due to evasion of miRNA-mediated repression. Supplementary Figure S3. Screening of APA factors that contribute to the PAS selection of RAC1 in UCB. Supplementary Figure S4. CSTF2 regulates colony formation and invasiveness abilities of shorter RAC1 isoform in UCB. Supplementary Table S1. PDUI value calculated from DaPars analysis of 15 pairs of UCB and adjacent normal bladder tissues. Supplementary Table S2. KEGG pathway analyses of APA genes identified from RNA-Seq. Supplementary Table S3. RAC1 genomic mutations identified from TCGA UCB database. Supplementary Table S4. Correlation between the expression of CSTF2 and clinicopathologic characteristics of UCB patients

Supplementary Methods, Supplementary Figure legends and Supplementary Table S1 to S4.

Down-regulation of miR-644a restores PITX2 expression in KYSE-410 cells. A, down-regulation of miR-644a significantly increased the luciferase activity that carried wt but not mt 3'-UTR of PITX2. B and C, down-regulation of miR-644a significantly increased PITX2 mRNA (B) and protein (C) levels of KYSE-410 cells. **P