In the two-level system of effective supply of public stadiums, institutional supply is the constraint of product supply, and product supply feeds back to the formation of institutional supply. The ...establishment and change of the government function supply system is the key to the efficiency of privatized product supply. Therefore, the government in the process of privatization of public stadiums and gymnasiums in our country will realize the corresponding and complete regulatory functions before entering, during access, during implementation and after exit.
Abstract
Background
Emerging evidence has shown that circular RNAs (circRNAs) play a crucial regulatory role in the occurrence and development of cancer. Exploring the roles and mechanisms of ...circRNAs in tumorigenesis and progression may help to identify new diagnostic markers and therapeutic targets. In the present study, we investigated the role and regulatory mechanism of hsa_circ_0004872 in gastric cancer (GC).
Methods
qRT-PCR was used to determine the expression of hsa_circ_0004872 in GC tissues and cells. EdU, CCK-8, transwell and scratch wound healing assays were used to assess the role of hsa_circ_0004872 in GC cell proliferation, invasion and migration, respectively. Subcutaneous and tail vein tumor injections in nude mice were used to assess the role of hsa_circ_0004872 in vivo. RIP assay, biotin-coupled probe pull-down assay, FISH and luciferase reporter assay were performed to confirm the relationship between hsa_circ_0004872 and the identified miRNA. ChIP assay, luciferase reporter assay and western blot were used to determine the direct binding of Smad4 to the promoter of the ADAR1 gene.
Results
In this study, we found that hsa_circ_0004872 was dramatically downregulated in GC tissues compared with adjacent noncancerous tissues. The expression level of hsa_circ_0004872 was associated with tumor size and local lymph node metastasis. Enforced expression of hsa_circ_0004872 inhibited the proliferation, invasion and migration of GC cells, whereas knockdown of hsa_circ_0004872 had the opposite effects. Nude mice experiments showed that ectopic expression of hsa_circ_0004872 dramatically inhibited tumor growth and metastasis in vivo. Moreover, we demonstrated that hsa_circ_0004872 acted as a “molecular sponge” for miR-224 to upregulate the expression of the miR-224 downstream targets p21 and Smad4. Importantly, we found that the RNA-editing enzyme ADAR1 inhibited hsa_circ_0004872 expression and further led to the upregulation of miR-224. Smad4, the downstream target of miR-224, could further affect hsa_circ_0004872 levels by directly binding to the promoter region of ADAR1 to inhibit ADAR1 expression.
Conclusions
Our findings showed that hsa_circ_0004872 acted as a tumor suppressor in GC by forming a negative regulatory loop consisting of hsa_circ_0004872/miR-224/Smad4/ADAR1. Thus, hsa_circ_0004872 may serve as a potential biomarker and therapeutic target for GC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent findings show that a subset of bacteria affiliated with Nitrospira, a genus known for its importance in nitrite oxidation for biological nutrient removal applications, are capable of complete ...ammonia oxidation (comammox) to nitrate. Early reports suggested that they were absent or present in low abundance in most activated sludge processes, and thus likely functionally irrelevant. Here we show the accumulation of comammox Nitrospira in a nitrifying sequencing batch reactor operated at low dissolved oxygen (DO) concentrations. Actual mainstream wastewater was used as influent after primary settling and an upstream pre-treatment process for carbon and phosphorus removal. The ammonia removal rate was stable and exceeded that of the treatment plant's parallel full-scale high DO nitrifying activated sludge reactor. 16S rRNA gene sequencing showed a steady accumulation of Nitrospira to 53% total abundance and a decline in conventional ammonia oxidizing bacteria to <1% total abundance over 400 + days of operation. After ruling out other known ammonia oxidizers, qPCR confirmed the accumulation of comammox Nitrospira beginning around day 200, to eventually comprise 94% of all detected amoA and 4% of total bacteria by day 407. Quantitative fluorescence in-situ hybridization confirmed the increasing trend and high relative abundance of Nitrospira. These results demonstrate that comammox can be metabolically relevant to nitrogen transformation in wastewater treatment, and can even dominate the ammonia oxidizing community. Our results suggest that comammox may be an important functional group in energy efficient nitrification systems designed to operate at low DO levels.
•Ammonia oxidation was dominated by comammox in a mainstream nitrification reactor.•Efficient nitrification at low DO concentrations of 0.2–1.0 mg/L.•Total Nitrospira increased in abundance to 53% of the overall microbial community.•Comammox Nitrospira increased in abundance to 4% of the overall microbial community.•Comammox may play an important role in low DO nutrient removal biotechnologies.
As central nodes in cardiomyocyte signaling, nuclear AKT appears to play a cardio-protective role in cardiovascular disease. Here we describe a circular RNA, circ-Amotl1 that is highly expressed in ...neonatal human cardiac tissue, and potentiates AKT-enhanced cardiomyocyte survival. We hypothesize that circ-Amotl1 binds to PDK1 and AKT1, leading to AKT1 phosphorylation and nuclear translocation. In primary cardiomyocytes, epithelial cells, and endothelial cells, we found that forced circ-Amotl1 expression increased the nuclear fraction of pAKT. We further detected increased nuclear pAKT in circ-Amotl1-treated hearts. In vivo, circ-Amotl1 expression was also found to be protective against Doxorubicin (Dox)-induced cardiomyopathy. Putative PDK1- and AKT1-binding sites were then identified
. Blocking oligonucleotides could reverse the effects of exogenous circ-Amotl1. We conclude that circ-Amotl1 physically binds to both PDK1 and AKT1, facilitating the cardio-protective nuclear translocation of pAKT.
Three RNA helicases - DDX42, DDX46 and DHX15 - are found to be associated with human U2 snRNP, but their roles and mechanisms in U2 snRNP and spliceosome assembly are insufficiently understood. Here ...we report the cryo-electron microscopy (cryo-EM) structures of the DDX42-SF3b complex and a putative assembly precursor of 17S U2 snRNP that contains DDX42 (DDX42-U2 complex). DDX42 is anchored on SF3B1 through N-terminal sequences, with its N-plug occupying the RNA path of SF3B1. The binding mode of DDX42 to SF3B1 is in striking analogy to that of DDX46. In the DDX42-U2 complex, the N-terminus of DDX42 remains anchored on SF3B1, but the helicase domain has been displaced by U2 snRNA and TAT-SF1. Through in vitro assays, we show DDX42 and DDX46 are mutually exclusive in terms of binding to SF3b. Cancer-driving mutations of SF3B1 target the residues in the RNA path that directly interact with DDX42 and DDX46. These findings reveal the distinct roles of DDX42 and DDX46 in assembly of 17S U2 snRNP and provide insights into the mechanisms of SF3B1 cancer mutations.
Contact toxicity assessments of six reduced risk insecticides were carried out to compare their selectivity and sensitivity toward the minute pirate bug Orius strigicollis and its prey Thrips ...hawaiiensis. Additionally, and their potential exposure risk were evaluated for O. strigicollis. The LR50 value of acetamiprid, emamectin benzoate, cyetpyrafen, and indoxacarb to T. hawaiiensis were 0.126, 2.093, 7.486, and 2.264 g a.i. ha−1, respectively, far less than the maximum field recommended rate (MFRR) for each. These four insecticides showed higher selectivity for predator and prey with selectivity ratio values of 37.3, 14.8, 22.1, and 119.3, respectively. However, the LR50 value of acetamiprid and emamectin benzoate were lower than MFRR, and unacceptable (approximately unacceptable for emamectin benzoate) risk to O. strigicollis in in-field, and the opposite results were shown in cyetpyrafen and indoxacarb. Although T. hawaiiensis was more sensitive to abamectin than O. strigicollis, the insecticide had poor selectivity for both test insects. The LR50 value of spirotetramat was more than 3 fold MFRR for T. hawaiiensis and O. strigicollis, showing extremely low contact toxicity and selectivity. In general, acetamiprid, emamectin benzoate, cyetpyrafen, and indoxacarb showed high bioactivity against T. hawaiiensis, but only cyetpyrafen and indoxacarb could be well compatible with O. strigicollis, the combination of two insecticides with O. strigicollis indicated a potential strategy for the efficient and safe control of T. hawaiiensis.
•Contact toxicity of six reduced-risk insecticides was assessed.•LR50 of four insecticides was less than the maximum field recommended rate.•These insecticides had high selectivity for O. strigicollis and T. hawaiiensis.•Risk of insecticides to O. strigicollis was acceptable except for acetamiprid.•Cyetpyrafen and indoxacarb in combination with O. strigicollis is promising in IPM.
Abstract RUNX3 is a transcriptional factor that has been shown to regulate protein-coding gene expression at the transcriptional level. However, the regulation of RUNX3 on miRNAs is not fully ...understood. In this study, we used miRNA microarray to identify the miRNAs that are regulated by RUNX3 and found that miR-29b showed the most up-regulation in RUNX3 over-expressed cells compared with the control cells. We used qRT-PCR to confirm the miRNA microarray results in several gastric cancer cells and found that RUNX3 could bind to the miR-29b promoter directly and cooperate with Smad3 to increase the promoter activity of miR-29b. In the clinical setting, both RUNX3 and miR-29b are down-regulated significantly in human gastric cancer tissues. A positive correlation between miR-29b and RUNX3 was found in the gastric cancer tissues. Additionally, we found that miR-29b suppressed the proliferation and metastasis of gastric cancer cells by directly targeting KDM2A. The miR-29b/KDM2A axis was involved in the RUNX3-mediated inhibition of gastric cancer cell proliferation and metastasis. Taken together, our results suggested that RUNX3-mediated up-regulation of miR-29b inhibited the proliferation and migration of gastric cancer cells by targeting KDM2A, representing a novel molecular mechanism for the tumor suppression action of RUNX3.
SWI/SNF remodelers play a key role in regulating chromatin architecture and gene expression. Here, we report the cryo-EM structure of the Saccharomyces cerevisiae Swi/Snf complex in a nucleosome-free ...state. The structure consists of a stable triangular base module and a flexible Arp module. The conserved subunits Swi1 and Swi3 form the backbone of the complex and closely interact with other components. Snf6, which is specific for yeast Swi/Snf complex, stabilizes the binding of the ATPase-containing subunit Snf2 to the base module. Comparison of the yeast Swi/Snf and RSC complexes reveals conserved structural features that govern the assembly and function of these two subfamilies of chromatin remodelers. Our findings complement those from recent structures of the yeast and human chromatin remodelers and provide further insights into the assembly and function of the SWI/SNF remodelers.
The F-box protein FBXO31, a component of the Skp1/Cul1/F-box (SCF) E3 ubiquitin ligase complex, plays an important regulatory role in neuronal development, stress response, and tumorigenesis. Our ...recent report indicates that FBXO31 functions as a tumor suppressor in gastric cancer, and the loss of FBXO31 protein is associated with a higher malignant phenotype and poorer prognosis. However, little is known about the underlying mechanism. In this study, FBXO31 inhibits gastric cancer progression by suppressing the epithelial-mesenchymal transition (EMT). FBXO31 overexpression decreases, whereas its inhibition increases, the protein level of the EMT transcription factor Snail1 (SNAI1), respectively. Further evidence demonstrates that FBXO31 interacts with Snail1 and mediates the ubiquitin- and proteasome-dependent degradation of Snail1 in gastric cancer. The F-box domain of FBXO31 and the phosphorylation of Snail1 are necessary for the molecular interaction between FBXO31 and Snail1. Mouse modeling experiments reveal that FBXO31 overexpression inhibits
colonization of gastric cancer cells. Furthermore, a highly significant negative correlation between FBXO31 and Snail1 is validated in human gastric cancer clinical specimens. Taken together, these findings identify Snail1 as a new target protein of FBXO31 in gastric cancer and substantiate a novel regulatory role of FBXO31 on gastric cancer progression and metastasis.
These findings demonstrate that FBXO31 exerts the tumor-inhibitory role in gastric cancer by ubiquitin-mediated degradation of Snail1, which represents a viable strategy of FBXO31 activators in the prevention and therapy of gastric cancer.
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Using bio-based antioxidants and industrial wastes to inhibit asphalt aging is a sustainable practice in the pavement industry. To investigate the inhibitory effects and potential mechanisms of ...phenolic compounds and crumb tire rubber on the aging deterioration of asphalt binders, the aging characteristics of base asphalt, catechin modified asphalt, and crumb rubber modified asphalt were evaluated using Fourier transform infrared spectroscopy and reactive molecular dynamics simulations. The results showed that both catechins and crumb rubber exerted resistance to asphalt aging and that the former performed better. Specifically, catechins block asphalt aging at the chemical level by providing active H atoms to react with O2 and free radicals, thus preventing them from oxidizing asphalt molecules. In contrast, crumb rubber exerts its antiaging properties mainly in physical aspects, firstly by limiting the movement of asphalt molecules to reduce the contact and reaction of asphalt with O2 and secondly by counteracting the aging-induced asphalt hardening through its own degradation, thus partially restoring the mechanical properties of aged asphalt. This study provides molecular insight into the antiaging mechanisms of natural phenolic compounds and rubber polymers and is expected to provide theoretical guidance for the development of targeted antiaging technologies for asphalt binders.
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