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Background Colorectal cancer (CRC) is one of the most common malignant tumours. The recurrence and metastasis of CRC seriously affect the survival rate of patients. Angiogenesis is an extremely important cause of tumour growth and metastasis. Circular RNAs (circRNAs) have been emerged as vital regulators for tumour progression. However, the regulatory role, clinical significance and underlying mechanisms still remain largely unknown. Methods High-throughput sequencing was used to analyse differential circRNAs expression in tumour and non-tumour tissues of CRC. In situ hybridization (ISH) and qRT-PCR were used to determine the level of circ3823 in CRC tissues and serum samples. Then, functional experiments in vitro and in vivo were performed to investigate the effects of circ3823 on tumour growth, metastasis and angiogenesis in CRC. Sanger sequencing, RNase R and Actinomycin D assay were used to verify the ring structure of circ3823. Mechanistically, dual luciferase reporter assay, fluorescent in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down experiments were performed to confirm the underlying mechanisms of circ3823. Results Circ3823 was evidently highly expressed in CRC and high circ3823 expression predicted a worse prognosis of CRC patients. Receiver operating characteristic curves (ROCs) indicated that the expression of circ3823 in serum showed high sensitivity and specificity for detecting CRC which means circ3823 have the potential to be used as diagnostic biomarkers. Functional experiments in vitro and in vivo indicated that circ3823 promote CRC cell proliferation, metastasis and angiogenesis. Mechanism analysis showed that circ3823 act as a competing endogenous RNA of miR-30c-5p to relieve the repressive effect of miR-30c-5p on its target TCF7 which upregulates MYC and CCND1, and finally facilitates CRC progression. In addition, we found that N6-methyladenosine (m6A) modification exists on circ3823. And the m6A modification is involved in regulating the degradation of circ3823. Conclusions Our findings suggest that circ3823 promotes CRC growth, metastasis and angiogenesis through circ3823/miR-30c-5p/TCF7 axis and it may serve as a new diagnostic marker or target for treatment of CRC patients. In addition, m6A modification is involved in regulating the degradation of circ3823.

A pre-metastatic niche is a microenvironment prepared for the colonization of circulating tumor cells in specific organs. Exosomes are extracellular vesicles with a variety of biological functions. Exosomes play an irreplaceable role in the development of pre-metastatic niches, and mainly function as communication medium. In this review, we analyzed the effects of exosomes on pre-metastatic niches from various perspectives, including inflammation, immune response, angiogenesis, organotropism, matrix remodeling and biomarker expression. In particular, exosomes express programmed death ligand 1 (PD-L1) and cause the immune escape of tumor cells. The immunomodulatory effects of exosomes and their potential in liquid diagnosis have drawn our attention. The potential value of exosomes and pre-metastatic niches will be realized in the field of immunity therapy.

The protein methyltransferase SET and MYND domain-containing protein 2 (SMYD2) is a transcriptional regulator that methylates histones and nonhistone proteins. As an oncogene, SMYD2 has been investigated in numerous types of cancer. However, its involvement in lung cancer remains elusive. The prognostic value of SMYD2 expression in lung adenocarcinoma (LUAD) was determined through bioinformatics analysis, reverse-transcription polymerase chain reaction, western blotting, and immunohistochemistry. The effect of SMYD2 on LUAD cell proliferation and metastasis was explored in vivo and in vitro, and the underlying mechanisms were investigated via RNA-seq, and chromatin immunoprecipitation-quantitative PCR. SMYD2 expression was significantly upregulated in LUAD cell lines and tissues. High SMYD2 expression was associated with shorter overall and disease-free survival in LUAD patients. Inhibition of SMYD2 with SMYD2 knockdown or AZ505 dramatically inhibited the proliferation, migration, and invasion ability of GLC-82 and SPC-A1 cells and remarkably reduced tumor growth in mice. Mechanically, SMYD2 may activate the transcription of ribosomal small subunit protein 7 (RPS7) by binding to its promoter. Following overexpression of SMYD2, the proliferation, migration, and invasion of cells increased, which was partially reversed by RPS7. Thus, SMYD2 might modulate tumorigenesis and metastasis mediated by RPS7 LUAD. SMYD2 might be a prognostic biomarker and therapeutic target in LUAD.

In advanced integrated circuit manufacturing, the quality of chemical mechanical polishing (CMP) is a key factor affecting chip performance and yield. Designers need to use CMP simulation tools to locate and analyze the defects in the layout after the CMP process. However, the advancement of process nodes and the increase in data volume presents a great challenge to the speed of graphical display of CMP simulation data. To solve this issue, we propose a solution that uses multi-threading technology to optimize both data reading and drawing. In the process of data reading, we employ OpenMP and memory mapping (Mmap) technology to achieve parallel reading of file segmentation and propose a fast-string conversion algorithm based on the properties of simulation data. In the process of data drawing, we propose an adaptive downsampling method for data graphical display that combines multi-threading and double buffering technology to enable the parallel drawing of layouts. The effectiveness of this method is verified by testing CMP simulation data of various scales. Compared to traditional methods, this approach improves reading efficiency by over 8 times and drawing efficiency by more than 10 times. Furthermore, it enhances the smoothness of interaction with the CMP simulation tool.

This study aimed to observe the safety and clinical efficacy of early application of ruxolitinib to prevent acute graft-versus-host disease (aGVHD) after alternative donor transplantation in acute leukemia. There were 57 patients undergoing allo-HSCT at the Affiliated Cancer Hospital of Zhengzhou University from July 2017 to October 2019. They were divided into control(16 patients) and ruxolitinib (41 patients) groups. For aGVHD prophylaxis, the control group received post-transplantation cyclophosphamide, antithymocyte globulin-Fresenius, cyclosporine A, and mycophenolate mofetil, while in the ruxolitinib group, ruxolitinib 5 mg/d in adults or 0.07–0.1 mg/(kg d) in children was administered from the day of neutrophil engraftment to 100 days post-transplantation based on control group. We found 55 patients had successful reconstitution of hematopoiesis; No significant difference was found in cGVHD, hemorrhagic cystitis, pulmonary infection, intestinal infection, Epstein-Barr virus infection, cytomegalovirus infection, relapse, death, and nonrelapse mortality. The incidences of aGVHD (50 vs. 22%, P  = 0.046) and grade II–IV aGVHD (42.9 vs. 12.2%, P  = 0.013) were significantly higher in the control group than in the ruxolitinib group. No significant differences were observed in overall survival ( P  = 0.514), disease-free survival ( P  = 0.691), and cumulative platelet transfusion within 100 days post-transplantation between two groups. This suggests early application of ruxolitinib can reduce the incidence and severity of aGVHD and patients are well tolerated.

Ventilation/perfusion (V/Q) matching represents a crucial indicator of lung function. The current for assessing V/Q in a clinical setting are inadequate for bedside monitoring purposes. They are characterised by invasiveness and an increased risk of infection. Accordingly, the present study was based on a high-performance electrical impedance tomography (EIT) system developed by our team, with the objective of exploring the feasibility of using it for non-invasive assessment of V/Q at the bedside. This was achieved by acquiring and imaging pulmonary blood flow pulsation signals and combining them with pulmonary ventilation impedance information. Continuous lung EIT imaging data were acquired at 40 fps through different body positions and breath-holding in anaesthetised domestic pigs (N = 8, 17.50 ± 1.51 kg). By analysing the blood flow pulsation impedance information, lung perfusion-related data were extracted and combined with lung ventilation impedance data to establish a pulsatility V/Q assessment method. Furthermore, the monitoring of pulmonary perfusion using hypertonic saline (5 ml of 10% NaCl) was employed as a control experiment. The results demonstrate that the V/Q results obtained through the utilisation of both methodologies exhibit a notable degree of variability in response to alterations in body position and the state of breath holding. The V/Q results obtained using the pulsatility method and the saline method were subjected to analysis using the Bland–Altman agreement test. During end-expiration breath-holding in the supine position, the results were as follows: 95% CI = 2.36% to 10.26%, bias = 6.309%. During end-inspiration breath-holding in the supine position, the results were as follows: 95% CI = 0.07% to 12.23%, bias = 6.150%. During end-expiration breath-holding in the prone position, the results were as follows: 95% CI = -0.40% to 14.43%, bias = 7.014%. During end-inspiration breath-holding in the prone position, the results were as follows: 95% CI = 1.92% to 11.17%, bias = 6.541%. Moreover, a Pearson correlation analysis revealed a significant correlation between the V/Q match% of the two methods ( r  = 0.7248; 95% CI = 0.50% to 0.86%; p  <  0.0001 ). Consequently, EIT imaging based on the pulsatility method is capable of assessing V/Q alterations resulting from diverse body positions and changes during breath-holding. This approach offers a novel concept for bedside monitoring of patients.

Cancer immunotherapies, such as checkpoint blockade of programmed cell death protein-1 (PD-1), represents a breakthrough in cancer treatment, resulting in unprecedented results in terms of overall and progression-free survival. Discovery and development of novel anti PD-1 inhibitors remains a field of intense investigation, where novel monoclonal antibodies (mAbs) and novel antibody formats (e.g., novel isotype, bispecific mAb and low-molecular-weight compounds) are major source of future therapeutic candidates. HLX10, a fully humanized IgG 4 monoclonal antibody against PD-1 receptor, increased functional activities of human T-cells and showed in vitro , and anti-tumor activity in several tumor models. The combined inhibition of PD-1/PDL-1 and angiogenesis pathways using anti-VEGF antibody may enhance a sustained suppression of cancer-related angiogenesis and tumor elimination. To elucidate HLX10’s mode of action, we solved the structure of HLX10 in complex with PD-1 receptor. Detailed epitope analysis showed that HLX10 has a unique mode of recognition compared to the clinically approved PD1 antibodies Pembrolizumab and Nivolumab. Notably, HLX10’s epitope was closer to Pembrolizumab’s epitope than Nivolumab’s epitope. However, HLX10 and Pembrolizumab showed an opposite heavy chain (HC) and light chain (LC) usage, which recognizes several overlapping amino acid residues on PD-1. We compared HLX10 to Nivolumab and Pembrolizumab and it showed similar or better bioactivity in vitro and in vivo , providing a rationale for clinical evaluation in cancer immunotherapy.

Background Acute pulmonary embolism represents the third most prevalent cardiovascular pathology, following coronary heart disease and hypertension. Its untreated mortality rate is as high as 20–30%, which represents a significant threat to patient survival. In view of the current lack of real-time monitoring techniques for acute pulmonary embolism, this study primarily investigates the potential of the pulsatility electrical impedance tomography (EIT) technique for the detection and real-time monitoring of acute pulmonary embolism through the collection and imaging of the pulsatile signal of pulmonary blood flow. Methods A before-and-after self-control experiment was conducted on anaesthetised domestic pigs ( N  = 12, 20.75 ± 2.56 kg). The changes in pulmonary perfusion caused by an acute pulmonary embolism (artificially induced) were monitored in real time using the pulsation method. This enabled the extraction of indicators such as Amplitude , Forward (Negative) Slope , and S ARC , which were used to assess the local pulmonary blood flow perfusion state. Furthermore, the degree of ventilation/perfusion matching in the lungs was evaluated concurrently with the analysis of the pulmonary ventilation area. Subsequently, a control verification was conducted utilising the conventional invasive hypertonic saline (5 ml 10% NaCl) contrast technique. Results The perfusion alterations subsequent to embolism in the pulsatility method are highly concordant with those observed in the hypertonic saline method, as evidenced by the imaging and indicator data. In particular, the perfusion area on the side of the embolism is markedly diminished, and the absolute values of all perfusion indicators are significantly reduced. Among these, Amplitude ( P < 0.001 ) and S ARC ( P < 0.001 ) exhibit the most pronounced alterations. Furthermore, the extracted indicators from regional ventilation demonstrated notable discrepancies, the V/Q match% ( P < 0.001 ) and Dead Space% ( P < 0.001 ) exhibited the most pronounced sensitivity to alterations in acute pulmonary embolism. Subsequently, a control verification was conducted utilising the hypertonic saline method, which revealed a high degree of consistency between the two methods in the detection of acute pulmonary embolism (Kappa = 0.75, P  < 0.05). Conclusions The EIT imaging method, which is based on the analysis of blood flow pulsation, has the potential to reflect in real time the changes in pulmonary blood flow that occur before and after an embolism. This provides a new avenue for the non-invasive real-time monitoring of patients with acute pulmonary embolism in a clinical setting.

Most reactors for non‐thermal plasma excitation are capacitive to pulse generators. The density and temperature of electrons in plasma are dominated by the discharging currents which are proportional to the pulse edges. However, adjusting the pulse edges is quite challenging since the switching speed and the inductance and capacitance in the discharging loops dominate them. This study proposes a drive circuit for solid‐state Marx generators with adjustable edges. The drive circuit controls the Miller plateau by adjusting the gate voltage amplitude to adjust both the rise time and fall time of pulses continuously and independently. The influence of the gate voltage on the Miller plateau and the rise time is studied. The feasibility is verified by both simulating and experimental results. An 8‐stage solid‐state Marx generator prototype was built, and 4.8‐kV pulses with a rise time in the range of 79 ns‐22.21 μs were obtained over capacitive loads. Adjusting pulse edges can control the current amplitudes in dielectric barrier discharge loads.

Objective To identify the prognostic indicators of esophageal adenocarcinoma (EAC) for future EAC diagnosis and treatment. Methods The EAC dataset from The Cancer Genome Atlas was screened for differentially expressed microRNAs (miRNAs) and mRNAs associated with EAC. Weighted gene coexpression network analysis was performed to cluster miRNAs or mRNA with similar expression patterns to identify the miRNAs or mRNA that are highly associated with EAC. Prognostic miRNAs for overall survival (OS) were identified using Cox proportional-hazards regression analysis and least absolute shrinkage and selection operator based on survival duration and status. Two types of miRNAs were selected to develop a prognostic signature model for EAC using multiple Cox regression analysis. Furthermore, the signature was validated using internal validation sets 1 and 2. The receiver operating characteristic curve and concordance index were used to evaluate the accuracy of the signature and validation sets. The expression of miR-421, miR-550a-3p, and miR-550a-5p was assessed using quantitative polymerase chain reaction (qPCR). The proliferation, invasion, and migration of EAC cells were assessed using CCK8 and transwell assays. The OS of target mRNAs was assessed using Kaplan–Meier analysis. Functional enrichment analysis of the target mRNAs was performed using Metascape. Results The prognostic signature and validation sets comprising mir-421 and mir-550a-1 had favorable predictive power in OS. Compared with the patients with EAC in the high-expression group, those assigned to the low-expression group displayed increased OS according to survival analysis. Differential and qPCR analysis showed that miR-421, miR-550a-3p, and miR-550a-5p were highly expressed in the EAC tissues and cell lines. Moreover, the downregulation of miR-421 and miR-550a-3p with inhibitor markedly suppressed the proliferation, invasion, and migration in OE33 cells compared with the negative control. A total of 20 target mRNAs of three miRNAs were predicted, among which seven target mRNAs— ASAP3 , BCL2L2 , LMF1 , PPM1L , PTPN21 , SLC18A2, and NR3C2 —had prognostic value; PRKACB , PDCD4 , RPS6KA5 , and BCL2L2 were enriched in the miRNA cancer pathway. Conclusion Prognostic indicators of EAC may be useful in future EAC diagnosis and treatment.