[Formation Mechanism and Source Analysis of Two Heavy Pollution Periods in Winter in a Central Plains City].

To reveal the process and cause of air pollution in winter in Zhengzhou, Zhengfangji Station was selected as the sampling point to discuss the concentration of air pollutants and the characteristics of meteorological parameters in December 2019, in Zhengzhou. The concentration changes in PM2.5 water-soluble ions, elements, and carbon components in different pollution stages were compared, and air quality model simulation results were used to analyze emissions from pollution sources and regional transmission during sampling of the PM2.5 mass concentration at the sampling point. The results showed that there was a slight difference in the process of formation and dissipation of the first and second heavy pollution occurrences, showing the characteristics of "slow accumulation, slow removal" and "slow accumulation, fast removal", respectively. The mass concentration of NO3-, SO42-, and NH4+ accounted for 41.5% and 46.2% of PM2.5, and the OC/EC ratios were 4.0 and 4.5 in the first and second heavy pollution periods, respectively. The formation of secondary aerosol particles was the main reason for the formation of heavy pollution. During the sampling period, the average contributions of local, eastern, southern, western, and northern regions to the PM2.5 concentration of the sampling point were 58.0%, 2.4%, 6.7%, 6.9%, and 12.7%, respectively. The first heavy pollution period was the result of combined locally sourced pollutant emission and externally sourced regional transmission, during which the contribution from western and southern regions and external industrial sources increased. The second heavy pollution period was mainly affected by the accumulation of local air pollutants, during which the contribution of traffic, dust, and coal-fired sources increased sharply, and the impact of external areas on the PM2.5 concentration of sampling point decreased.

MiR-486 promotes proliferation and suppresses apoptosis in myeloid cells by targeting Cebpa in vitro.

The monocytic MDSC (M-MDSC) is one of the major types of MDSCs, which play important roles in suppression of antitumor immunity. However, the mechanisms underlying how M-MDSCs so heavily accumulate in patients with cancer are still poorly understood. The purpose of this study was to identify miRNAs that regulate the proliferation and differentiation of M-MDSCs. Microarray analysis was performed to identify differentially expressed miRNAs between tumor-induced M-MDSCs (TM-MDSCs) and their counterparts from tumor-free mice. The miRNAs and their target genes that regulate the proliferation and differentiation of myeloid cells were predicted by bioinformatics analysis and validated by RT-qPCR. Luciferase reporter assays were used to analyze the relationships between miRNAs and target genes. Overexpression of candidate miRNAs and target genes in myeloid cells was conducted to verify their functions in cell proliferation, differentiation, and apoptosis. Our data showed that miR-486 was overexpressed in TM-MDSCs. Cebpa was predicted to be one of the target genes of miR-486 that regulates the proliferation of myeloid cells. Expression of Cebpa was inversely correlated with miR-486 in TM-MDSCs, and we found that overexpression of miR-486 suppressed the expression of Cebpa in both 293T cells determined by luciferase reporter assays and in myeloid cells determined by RT-qPCR. Overexpression of miR-486 promoted proliferation and suppressed apoptosis in myeloid cells, as opposed to overexpression of Cebpa, which promoted the opposing phenotype. Overexpression of either miR-486 or Cebpa inhibited differentiation of myeloid cells. This study indicates that miR-486 promotes proliferation and suppresses apoptosis in myeloid cells by targeting Cebpa in vitro, suggesting that miR-486 and Cebpa might be involved in the expansion of TM-MDSCs in tumor-bearing mice.

Arsenic trioxide inhibits tumor-induced myeloid-derived suppressor cells and enhances T-cell activity.

Myeloid-derived suppressor cells (MDSCs), one of the major orchestrators of the immunosuppressive network, are associated with immune suppression and considered a prime target for cancer immunotherapy. At present, various strategies have been explored to deplete and/or inactivate MDSCs in vivo. In this study, we investigated the effect of arsenic trioxide (ATO) on MDSCs derived from tumor-bearing mice. This study examined the in vitro and in vivo effects of ATO administration on MDSCs from C57/j mice bearing either the B16 or H22 tumor. The MDSCs were then characterized for phenotype, gene expression and function. Administration with ATO in vitro significantly induced MDSC differentiation, inhibited their proliferation and triggered apoptosis. Treatment with ATO in these murine tumor models significantly inhibited tumor growth and splenomegaly, decreased the percentages of MDSCs in the spleen, promoted their differentiation, reduced tumor necrosis factor-α and interleukin-10 levels and weakened the immune inhibition activity of MDSCs on T cells. In addition, we observed the underlying mechanism involved in the regulation of MDSCs by ATO, which included a panel of cytokines and signaling pathways. The findings showed the immunoregulatory effects of ATO by inducing apoptosis, promoting differentiation and inhibiting the function of MDSCs, suggesting that ATO has potential clinical benefit as it selectively attenuates MDSC-induced immunosuppression.

MicroRNA expression profiles of granulocytic myeloid­derived suppressor cells from mice bearing Lewis lung carcinoma.

Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous myeloid cells that can suppress antitumor immunity. MDSCs are divided into granulocytic (G­MDSCs) and monocytic subsets. In the present study, the microRNA profiles of the G­MDSCs were determined and the differential expression of microRNAs between G­MDSCs from tumor­bearing mice and tumor­free mice was examined. The number of G­MDSCs in spleens of Lewis lung carcinoma (LLC)­bearing mice was ~6­fold higher than in spleens of normal mice (13.54±1.74% vs. 2.14±1.44%; P<0.01) and G­MDSCs account for about 72.9% of all MDSCs. The microRNA (miRNA) profiles of the G­MDSCs from spleen of LLC­bearing mice were obtained using a microRNA microarray and compared with their counterparts from spleens of tumor­free mice. A total of 43 miRNAs with >1.3­fold increased or decreased change were differentially expressed between the experimental and control group mice. The levels of nine of these differentially expressed miRNAs, miRNA­468 (miR­486), miR­192, miR­128, miR­125a, miR­149, miR­27a, miR­125b, miR­350 and miR­328, were also analyzed by RT­qPCR to validate the microarray data. The concordance rate between the results tested by the two methods was 88.9%. Bioinformatics analyses revealed that these miRNAs may act on various target genes, including Adar, Pik3r1, Rybp and Rabgap1, to regulate the survival, differentiation and the function of tumor­induced granulocytic MDSCs. The results revealed microRNAs and potential targets that may be vital for regulating survival, differentiation and function of G­MDSCs induced by LLC. Further investigation should be performed to clarify the roles of these microRNAs in regulating LLC­induced granulocytic MDSCs and the target genes that mediate their functions.

The origin of segmentation motor activity in the intestine.

The segmentation motor activity of the gut that facilitates absorption of nutrients was first described in the late 19th century, but the fundamental mechanisms underlying it remain poorly understood. The dominant theory suggests alternate excitation and inhibition from the enteric nervous system. Here we demonstrate that typical segmentation can occur after total nerve blockade. The segmentation motor pattern emerges when the amplitude of the dominant pacemaker, the slow wave generated by interstitial cells of Cajal associated with the myenteric plexus (ICC-MP), is modulated by the phase of induced lower frequency rhythmic transient depolarizations, generated by ICC associated with the deep muscular plexus (ICC-DMP), resulting in a waxing and waning of the amplitude of the slow wave and a rhythmic checkered pattern of segmentation motor activity. Phase-amplitude modulation of the slow waves points to an underlying system of coupled nonlinear oscillators originating in the networks of ICC.

Neurogenic and myogenic properties of pan-colonic motor patterns and their spatiotemporal organization in rats.

BACKGROUND AND AIMS: Better understanding of intrinsic control mechanisms of colonic motility will lead to better treatment options for colonic dysmotility. The aim was to investigate neurogenic and myogenic control mechanisms underlying pan-colonic motor patterns. METHODS: Analysis of in vitro video recordings of whole rat colon motility was used to explore motor patterns and their spatiotemporal organizations and to identify mechanisms of neurogenic and myogenic control using pharmacological tools. RESULTS: Study of the pan-colonic spatiotemporal organization of motor patterns revealed: fluid-induced or spontaneous rhythmic propulsive long distance contractions (LDCs, 0.4-1.5/min, involving the whole colon), rhythmic propulsive motor complexes (RPMCs) (0.8-2.5/min, dominant in distal colon), ripples (10-14/min, dominant in proximal colon), segmentation and retrograde contractions (0.1-0.8/min, prominent in distal and mid colon). Spontaneous rhythmic LDCs were the dominant pattern, blocked by tetrodotoxin, lidocaine or blockers of cholinergic, nitrergic or serotonergic pathways. Change from propulsion to segmentation and distal retrograde contractions was most prominent after blocking 5-HT3 receptors. In the presence of all neural blockers, bethanechol consistently evoked rhythmic LDC-like propulsive contractions in the same frequency range as the LDCs, indicating the existence of myogenic mechanisms of initiation and propulsion. CONCLUSIONS: Neurogenic and myogenic control systems orchestrate distinct and variable motor patterns at different regions of the pan-colon. Cholinergic, nitrergic and serotonergic pathways are essential for rhythmic LDCs to develop. Rhythmic motor patterns in presence of neural blockade indicate the involvement of myogenic control systems and suggest a role for the networks of interstitial cells of Cajal as pacemakers.