CD44 is a potential immunotherapeutic target and affects macrophage infiltration leading to poor prognosis.

CD44 plays a key role in the communication of CSCs with the microenvironment and the regulation of stem cell properties. UALCAN was used to analyze the expression of CD44 in bladder cancer (BLCA) and normal tissue. The UALCAN was utilized to analyze the prognostic value of CD44 in BLCA. The TIMER database was used to explore the relationship between CD44 and PD-L1; CD44 and tumor-infiltrating immune cells. The regulatory effect of CD44 on PD-L1 was verified by cell experiments in vitro. IHC confirmed the results of the bioinformatics analysis. GeneMania and Metascape were used to analyze protein-protein interaction (PPI) investigations and functional enrichment analysis. We found that BLCA patients with high CD44 expression had worse survival than those with low CD44 expression (P < 0.05). IHC and the TIMER database results showed that CD44 expression was positively correlated with PD-L1 expression (P < 0.05). At the cellular level, the expression of PD-L1 was significantly inhibited after CD44 expression was inhibited by siRNA. Immune infiltration analysis showed that CD44 expression levels in BLCA were significantly correlated with immune infiltration levels of different immune cells. IHC staining results further confirmed that the expression of CD44 in tumor cells was positively associated with the number of CD68+ macrophages and CD163+ macrophages (P < 0.05). Our results suggest that CD44 is a positive regulator of PD-L1 in BLCA and may be a key regulator of tumor macrophages infiltration and may be involved in M2 macrophage polarization. Our study provided new insights into the prognosis and immunotherapy of BLCA patients through macrophage infiltration and immune checkpoints.

Dioscin modulates macrophages polarization and MDSCs differentiation to inhibit tumorigenesis of colitis-associated colorectal cancer.

It has been reported that colitis is one of risk factors in colorectal cancer (CRC). Intervention of intestinal inflammation and in the early stage of tumorigenesis is of great significance to control the incidence and mortality of CRC. In recent years, natural active products of traditional Chinese medicine have been confirmed that they had made great progress in disease prevention. Here, we showed that Dioscin, a natural active product of Dioscorea nipponica Makino, inhibited initiation and tumorigenesis of AOM/DSS-induced colitis-associated colon cancer (CAC), including alleviating colonic inflammation, improving intestinal barrier function and decreasing tumor burden. In addition, we also explored the immunoregulatory effect of Dioscin on mice. The results showed that Dioscin modulated M1/M2 macrophages phenotype in spleen and decreased monocytic myeloid-derived suppressor cells (M-MDSCs) population in blood and spleen of mice. The in vitro assay demonstrated that Dioscin promoted M1 as well as inhibited M2 macrophages phenotype in LPS- or IL-4-induced bone marrow-derived macrophages (BMDMs) model. Based on the plasticity of MDSCs and its ability to differentiate into M1/M2 macrophages, we here found that Dioscin increased M1- and decreased M2-like phenotype during the process of MDSCs differentiation in vitro, suggesting Dioscin promoted MDSCs differentiate into M1 as well as inhibited its differentiation into M2 macrophages. Taken together, our study indicated that Dioscin had the inhibitory effect on the initial of tumorigenesis at early stage of CAC via the ant-inflammatory effect, which provided a natural active candidate for effective prevention of CAC.

Research on a step delay method in sequential equivalent time sampling (ETS).

Sequential equivalent time sampling (ETS) has been extensively used in data acquisition instruments (e.g., sampling oscilloscopes and time domain reflectometers). A novel step delay method is proposed based on the frequency difference to obtain a higher sampling rate in sequential ETS. It is different from the classic step delay methods and is capable of increasing the sampling rate. The sampling clock and the repetitive signal are taken as examples in this study. The time-frequency conversion relationship indicates that a fine step delay will be generated in the time domain if there is a frequency difference between the two in the frequency domain. The core of the proposed method is the selection of the appropriate frequency difference (step delay) according to the desired equivalent sampling rate. Two experiments were performed to verify the proposed method. The feasibility of the proposed method is verified using a digital storage oscilloscope. Four cases are examined in the experiment, and the final equivalent sampling rate is obtained as 5 PS/s for the equivalent sampling of a 4.999 995 GHz (or higher) signal. A data acquisition system with a 10 MS/s real-time sampling rate is designed to verify the feasibility of the proposed method, obtaining a theoretical equivalent sampling rate of 585 GS/s. The theoretical equivalent sampling rate and the examined equivalent sampling rate are consistent. The equivalent sampling waveform and real-time sampling waveform of a 1 GHz signal are compared, and the comparison result suggests that the proposed method can acquire more waveform information. The proposed method obtains a high equivalent sampling rate for repetitive signals, and techniques (e.g., oversampling) are given to obtain higher vertical resolution. The proposed method, combined with a sample-and-hold amplifier, can also achieve a higher analog bandwidth.