Accumulating evidence indicates that circular RNAs (circRNAs) act as microRNA (miRNA) sponges to directly inhibit specific miRNAs and alter their ability to regulate gene expression at the ...post-transcriptional level; this mechanism is believed to occur in various cancers. However, the expression level, precise function and mechanism of circ_001680 in colorectal carcinoma (CRC) are largely unknown.
qRT-PCR was used to detect the expression of circ_001680 and miR-340 in human CRC tissues and their matched normal tissues. Bioinformatics analyses and dual-fluorescence reporter assays were used to evaluate whether circ_001680 could bind to miR-340. Circ_001680 overexpression and knockdown cell lines were constructed to investigate the proliferation and migration abilities in vivo and in vitro through function-based experiments, including CCK8, plate clone formation, transwell, and wounding healing assays. The relationships among circ_001680, miR-340 and BMI1 were investigated by bioinformatics analyses, dual-fluorescence reporter system, FISH, RIP and RNA pull down assays. Sphere forming assays and flow cytometry analyses were used to assess the effect of circ_001680 on the stemness characteristics of CRC cells.
Circ_001680 was more highly expressed in of CRC tissue than in matched adjacent normal tissues from the same patients. Circ_001680 was observed to enhance the proliferation and migration capacity of CRC cells. Furthermore, dual-fluorescence reporter assays confirmed that circ_001680 affects the expression of BMI1 by targeting miR-340. More importantly, we also found that circ_001680 could promote the cancer stem cell (CSC) population in CRC and induce irinotecan therapeutic resistance by regulating the miR-340 target gene BMI1.
Our results demonstrated that circ_001680 is a part of a novel strategy to induce chemotherapy resistance in CRC through BMI1 upregulation. Moreover, circ_001680 may be a promising diagnostic and prognostic marker to determine the success of irinotecan-based chemotherapy.
Background and objectives Trastuzumab is an important targeted drug for HER2-positive gastric cancer. The treatment efficacy of a more cost-effective and accessible trastuzumab biosimilar, HLX02, was ...not well investigated, especially when combined with antiangiogenic treatment. In addition, the tumour microenvironment detected by functional MRI was still unclear during treatment. This study attempts to evaluate the therapeutic effect of antiangiogenic agents combined with HLX02 in a HER2-positive gastric cancer xenograft model and to detect microenvironmental changes using intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). Materials and methods We subcutaneously injected MKN-45 human gastric cancer cells into BALB/C nude mice to establish a tumour model. Twenty-eight mice were divided into four groups and treated with saline (Group 1), Endostar (Group 2), trastuzumab biosimilar HLX02 (Group 3), or the combination of Endostar and HLX02 (Group 4). We then performed IVIM-DWI before and at different time points after treatment. HE, HER2, TUNEL, E-cadherin staining, and alpha-SMA and CD31 double-staining were used to confirm the pathological changes. Results Group 4 demonstrated the smallest tumour volume at the end of treatment. The D value in Group 4 increased more dramatically, with the highest value on Day 20, compared with the other groups. Perfusion-related parameters (D* and f values) in Groups 2 and 4 increased initially and reversed after Day 10. Group 4 showed the lowest CD31 and HER2 and the highest TUNEL- and E-cadherin-positive staining rates. The D value was positively correlated with TUNEL but negatively correlated with HER2 staining. The D* and f values had positive correlations with CD31 and E-cadherin expression and the vessel maturity index. Conclusions The trastuzumab biosimilar drug HLX02 exhibited good treatment efficacy in HER2-positive gastric cancer, especially when combined with Endostar. IVIM-DWI can noninvasively monitor the process of vascular normalization and reflect the treatment effect early at the molecular level. Keywords: HLX02, IVIM-DWI, Gastric cancer, HER2, Endostar, Vascular normalization
A new adsorbent with chromium removal function was synthesized by carbon thermal method using iron-containing waste Fenton sludge and carbon-containing solid waste fly ash to treat high pH scoring ...wastewater generated from industrial processes. The results showed that the adsorbent used T = 273.15 K, pH = 10, t = 1200 min, C
= 100 mg/L, had a removal rate of Cr(VI) of more than 80%, and the adsorption capacity could reach 393.79 mg/g. The characterization results show that the synthesized mesoporous nitrogen-doped composite material has a large specific surface area and mesoporous structure, and the surface of the material is rich in oxygen-containing functional groups and active sites. Compared with other studies, the adsorption capacity of the material is larger, which indicates that the removal effect of Cr(VI) in this study is better. The adsorption kinetic results show that the adsorption follows a pseudo second kinetic model, and the adsorption process is a chemisorption involving electron sharing or electron exchange. This experiment designed a simple method to synthesize mesoporous nitrogen-doped composites using industrial solid waste, with raw materials from cheap and easily available industrial solid waste, and solved the dual problems of heavy metals in wastewater and solid waste, providing a new idea for the resource utilization of Fenton sludge while not producing secondary pollution.
In order to achieve the purposes of better energy saving and lower fuel consumption under the condition in which load changes frequently and fluctuates dramatically, the energy-saving control ...strategy of power system is put forward in a hydraulic surface drilling rig. The structure of power system and working conditions of hydraulic surface drilling rigs are described. The mathematical models of the external characteristic for engine, variable pump, and air screw compressor in hydraulic surface drilling rig are presented in detail. Then the control strategy of power system and the fuzzy PID control algorithm to implement this strategy are proposed to control the engine speed in various working states. The simulation analysis and experimental investigation are carried out to study the fuel consumption in the typical operating conditions by using energy-saving control strategy. Results show that the energy-saving control strategy can reduce fuel consumption for the hydraulic surface drilling rig while ensuring that the system performance is not sacrificed.
Pancreatic cancer (PACA), which is characterized by an immunosuppressive nature, remains one of the deadliest malignancies worldwide. Aberrant DNA methylation (DNAm) reportedly influences tumor ...immune microenvironment. Here, we evaluated the role of DNA methylation driven genes (MDGs) in PACA through integrative analyses of epigenomic, transcriptomic, genomic and clinicopathological data obtained from TCGA, ICGC, ArrayExpress and GEO databases. Thereafter, we established a four-MDG signature, comprising GPRC5A, SOWAHC, S100A14, and ARNTL2. High signature risk-scores were associated with poor histologic grades and late TNM stages. Survival analyses showed the signature had a significant predictive effect on OS. WGCNA revealed that the signature may be associated with immune system, while high risk-scores might reflect immune dysregulation. Furthermore, GSEA and GSVA revealed significant enrichment of p53 pathway and mismatch repair pathways in high risk-score subgroups. Immune infiltration analysis showed that CD8+ T cells were more abundant in low score subgroups, while M0 macrophages exhibited an opposite trend. Moreover, negative regulatory genes of cancer-immunity cycle (CIC) illustrated that immunosuppressors TGFB1, VEGFA, and CD274 (PDL1) were all positively correlated with risk-scores. Furthermore, the four signature genes were negatively correlated with CD8+ lymphocytes, but positively associated with myeloid derived suppressor cells (MDSC). Conversely, specimens with high risk-scores exhibited heavier tumor mutation burdens (TMB) and might show better responses to some chemotherapy and targeted drugs, which would benefit stratification of PACA patients. On the other hand, we investigated the corresponding proteins of the four MDGs using paraffin-embedded PACA samples collected from patients who underwent radical surgery in our center and found that all these four proteins were elevated in cancerous tissues and might serve as prognostic markers for PACA patients, high expression levels indicated poor prognosis. In conclusion, we successfully established a four-MDG-based prognostic signature for PACA patients. We envisage that this signature will help in evaluation of intratumoral immune texture and enable identification of novel stratification biomarkers for precision therapies.
Hydraulic vibration excitation has been widely regarded as a promising method of excitation because of its high power density and large output force. However, the alternating pressure in the ...hydraulic vibration exciter could cause the pilot-operated relief valve (PRV) to open abnormally, which presents a new challenge to the normal operation of the PRV. To determine the abnormal opening characteristics of the PRV under alternating pressure, the effects of structure parameters of the PRV (including diameters of orifices 1 and 2, volume of the pilot valve inlet, volume of the main valve spring chamber, area ratio of the main spool, and main spring pre-compression force and stiffness) on its abnormal opening displacement under alternating pressure were numerically investigated. The calculation results indicate that the abnormal opening of the PRV will be effectively decreased by appropriately increasing the diameter of orifice 1, decreasing the pilot valve inlet and main valve spring chamber volumes, and increasing the area ratio of the main spool and the main spring pre-compression force. The influence of the orifice 2 diameter on the abnormal opening of the PRV is dependent on the diameter range of orifice 1. The reasonable diameters of orifices 1 and 2 are in the range of 0.8-1.2 mm. The influence of the main valve spring chamber volume is more significant than the pilot valve inlet volume. The influence of the main spring stiffness is not significant.
Hydraulic vibration exciter (HVE) is an important basic equipment for modern industrial production and scientific experiments. However, when HVE is working, the inevitable alternating pressure in its ...hydraulic system could give rise to unreliable work of its pilot-operated relief valve (PRV). The present paper aims to determine the abnormal opening mechanism of the PRV under alternating pressure. In this work, a mathematical model of the PRV was presented and validated, and the essential reason for the abnormal opening of the valve was discovered. The influence of the characteristic parameters of alternating pressure on the abnormal opening was investigated. The results show that the characteristic parameters of alternating pressure, including the pressure gradient, pressure amplitude, and pressure valley value, have a significant influence on the abnormal opening of the valve. The abnormal opening can be significantly improved by decreasing the pressure gradient and pressure amplitude, and increasing the pressure valley value.
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Modification methods for sludge-based biochar are often complex and generally ineffective. In this study, sludge-based biochars were prepared at low cost using a simple air ...roasting-oxidation modification method and the adsorption performance on U(VI) was investigated. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) results together indicated that more carbon–oxygen functional groups were formed on the surface of oxidized biochar (OBC) compared to unoxidized biochar (BC). The adsorption performance of 550-OBC (biochar oxidized at 550 °C) on U(VI) was explored in batch experiments. The maximum adsorption capacity was up to 490.2 mg/g at 25 °C and pH 6, exceeding most of the reported biochars. 550-OBC also showed good adsorption performance at low U(VI) concentration, with 96% removal at pH 6 and an initial U(VI) concentration of 1 mg/L. Density functional theory (DFT) calculations indicated that the H-bond length between the solvated U(VI) and functional groups on the OBC was about 1.7 Å, which forms stronger H-bonds between them compared to that between U(VI) and BC (4.21 Å), and the adsorption energy value for this complex was highly negative −31.82 kcal/mol. In addition, 550-OBC exhibited high selectivity for U(VI) adsorption and excellent regeneration performance, making it a cost-effective and high-performance adsorbent.
Biochar derived from municipal sludge can be applied to adsorption. But it usually requires activation and pickling due to the generation of impurities such as metal oxide particles, which is ...uneconomical. Here, a facile strategy, acidification-one-step calcination, was developed and sludge-based Fe–C materials with good Cr(VI) removal effect were obtained by regulating the amount of hydrochloric acid. The results show that the adsorption capacity of Fe/C-5 (the best sample) for Cr(VI) was 150.84 mg g−1. According to the Langmuir isotherm and pseudo-second-order kinetic model, the removal of Cr(VI) by Fe/C-5 is spontaneous and endothermic chemisorption process. In addition, Fe/C-5 has good ability to remove Cr(VI) under the interference of coexisting ions, and has good cycle stability. The removal of Cr(VI) by Fe/C-5 is considered to be synergistic process of adsorption and reduction. The Fe atoms were highly dispersed in Fe/C-5 and tightly bonded with C atoms, which not only strengthened the Cr(VI) adsorption by electrostatic attraction, but also activated the C atoms in the biochar material, so that the C atoms can reduce Cr(VI) to Cr(III) under acidic conditions. This may be due to the fact that acid pretreatment converted the iron in municipal sludge in the form of Fe–O/OH to free Fe3+ and entered the C lattice during the calcination process. In this work, Fe–C materials with excellent Cr(VI) adsorption capacity were prepared by one-step calcination method, which has important reference significance for the resource utilization of municipal sludge.
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•Fe/C materials were prepared by one-step calcination of acidified municipal sludge.•The Fe3+ are highly dispersed in Fe/C-5 rather than in the form of cluster.•Fe/C materials removed Cr(VI) by adsorption and reduction synergistically.
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