Inflammatory response in mouse lungs to haze episodes under different backgrounds of particulate matter exposure.

Particulate matter (PM) toxicity has mostly been investigated through in vitro exposure or tracheal infusion in animal models. However, given the complexity of ambient conditions, most animal studies do not mimic real-life PM exposure. In this work, we established a novel integrated exposure model to study the dynamic inflammatory response and defense strategies in ambient PM-exposed mice. Three groups of male C57BL/6 mice were kept in three chambers with pre-exposure to filtered air (FA), unfiltered air (UFA), or the air with a low PM concentration (PM2.5 ≤ 75 µg/m3) (LPM), respectively, for 37 days. Then all three groups of mice were exposed to haze challenge for 3 days, followed by exposure in filtered air for 7 days to allow recovery. Our results suggest that following a haze challenge, the defense strategies of mice of filtered air (FA) and low PM (LPM) groups comprised a form of "counterattack", whereas the response of the unfiltered air (UFA) group could be viewed as a "silence". While the latter strategy protected the lung tissues of mice from acute inflammatory damage, it also foreshadowed the development of chronic inflammatory diseases. These findings contribute to explaining previously documented PM-associated pathogenic mechanisms.

Ontogeny of RORγt+ cells in the intestine of newborns and its role in the development of experimental necrotizing enterocolitis.

BACKGROUND: Neonates possess an immature and plastic immune system, which is a major cause of some diseases in newborns. Necrotizing enterocolitis (NEC) is a severe and devastating intestinal disease that typically affects premature infants. However, the development of intestinal immune cells in neonates and their roles in the pathological process of NEC have not been elucidated. RESULTS: We examined the ontogeny of intestinal lamina propria lymphocytes in the early life of mice and found a high percentage of RORγt+ cells (containing inflammatory Th17 and ILC3 populations) during the first week of life. Importantly, the proportion of RORγt+ cells of intestinal lamina propria further increased in both NEC mice and patients tissue than the control. Furthermore, the application of GSK805, a specific antagonist of RORγt, inhibited IL-17A release and ameliorated NEC severity. CONCLUSIONS: Our data reveal the high proportion of RORγt+ cells in newborn mice may directly contribute to the development of NEC.

Dynamics of TCR repertoire and T cell function in COVID-19 convalescent individuals.

SARS-CoV-2 outbreak has been declared by World Health Organization as a worldwide pandemic. However, there are many unknowns about the antigen-specific T-cell-mediated immune responses to SARS-CoV-2 infection. Here, we present both single-cell TCR-seq and RNA-seq to analyze the dynamics of TCR repertoire and immune metabolic functions of blood T cells collected from recently discharged COVID-19 patients. We found that while the diversity of TCR repertoire was increased in discharged patients, it returned to basal level ~1 week after becoming virus-free. The dynamics of T cell repertoire correlated with a profound shift of gene signatures from antiviral response to metabolism adaptation. We also demonstrated that the top expanded T cell clones (~10% of total T cells) display the key anti-viral features in CD8+ T cells, confirming a critical role of antigen-specific T cells in fighting against SARS-CoV-2. Our work provides a basis for further analysis of adaptive immunity in COVID-19 patients, and also has implications in developing a T-cell-based vaccine for SARS-CoV-2.

SIRT1-ZEB1-positive feedback promotes epithelial-mesenchymal transition process and metastasis of osteosarcoma.

Osteosarcoma is the most common malignant bone cancer that mainly affects children and young adults. Recently, the NAD+ -dependent deacetylase, sirtuin 1 (SIRT1), has been reported to play a key role in the development of malignant tumors. The study aimed to investigate the role of SIRT1 in osteosarcoma and explore its underlying oncogenic mechanisms. The prognostic value of SIRT1 in osteosarcoma was assessed through detection of SIRT1 expression based on osteosarcoma biopsy tissue. Then, to further investigate the effect of SIRT1 in osteosarcoma, osteosarcoma cells were treated with small interfering RNA SIRT1 and overexpressed SIRT1 to detect the cell migration, invasion, and epithelial-mesenchymal transition (EMT). The levels of SIRT1 expression were significantly higher in osteosarcoma tissues than those in adjacent normal tissues, and the SIRT1 protein level may be coupled with metastatic and poor prognosis risk in patients with osteosarcoma. Moreover, SIRT1 silencing inhibited the migration as well as invasion ability of osteosarcoma cells in vitro, and SIRT1 upregulation reversed those effects. Finally, we found that SIRT1-ZEB1-positive feedback enhanced the EMT process and metastasis of osteosarcoma. Altogether, the results of the current study revealed that high levels of SIRT1 might be a biomarker for a high metastatic rate in patients with osteosarcoma, which suggested that inhibition of SIRT1 might be promising for the therapeutics of osteosarcoma.

MicroRNA-503 represses epithelial-mesenchymal transition and inhibits metastasis of osteosarcoma by targeting c-myb.

Deregulated expression of miRNAs contributes to the development of osteosarcoma. Our previous study has showed that miR-503 was downregulated in osteosarcoma tissues. However, the mechanism of the miR-503 in osteosarcoma development still remains largely undefined. In our study, we found that miR-503 overexpression suppressed cell invasion and migration and inhibited epithelial-to-mesenchymal transition (EMT) of MG-63. Furthermore, we identified that c-myb, an oncogene, was a direct target of miR-503. Moreover, overexpression of c-myb could rescue miR-503-suppressed invasion and EMT. The expression of c-myb was upregulated in osteosarcoma cell lines. Therefore, we conclude that high miR-503 expression suppressed osteosarcoma cell mobility and EMT through targeting c-myb, and this may serve as a therapeutic target.

Column-mode fluoride removal from aqueous solution by magnesia-loaded fly ash cenospheres.

Column experiments in a fixed bed reactor packed with a certain amount of magnesia-loaded fly ash cenospheres (MLC) were conducted to examine the effects of adsorbent mass, flow velocities, influent concentrations and coexisting anions on fluoride removal. The breakthrough time increased with an increase in adsorbent mass, but decreased with increasing influent fluoride concentration. The exhaustion time decreased with the increase in the influent fluoride concentration. The capacity at the breakthrough point increased with an increase in adsorbent mass, flow velocity and the influent fluoride concentration. The capacity at the exhaustion point increased with an increase in flow velocity, but showed no specific trend with an increase in the initial fluoride concentration. The bed volumes at breakthrough point increased with an increase in adsorbent mass, flow velocity and the influent fluoride concentration. The empty bed contact time decreased with an increase in flow velocity. The coexisting anions reduced the adsorption capacity of the fixed bed reactor in the order: mixture of all three anions > dihydric phosphate > nitrate > sulfate. The adsorbent exhaustion rate decreased with the increase in flow velocity and adsorbent mass, whereas it increased with increasing influent fluoride concentration. Columns with large amounts of MLC are preferable in order to obtain optimal results during the adsorption process, and the higher the flow velocity, the better the column performance. The Bohart and Adams model and the Thomas model were applied to the experimental results. Column adsorption was reversible and the regeneration operation was accomplished by pumping 0.2 M NaOH through the loaded MLC column.

Comparison of two adsorbents for the removal of pentavalent arsenic from aqueous solutions.

Two adsorbents, magnesia-loaded fly ash cenospheres (MGLC) and manganese-loaded fly ash cenospheres (MNLC), were prepared by wet impregnation of fly ash cenospheres with MgCl(2) solution or a mixed solution of MnCl(2) and KMnO(4), respectively. Their physicochemical properties were characterized by scanning electron microscopy, X-ray diffractometry, X-ray fluorescence spectrometry, and Fourier transform infrared spectrometry. Sorption experiments were conducted to examine the effects of adsorbent dosage, pH, time, temperature, ionic strength and competing anions on As(V) removal by MGLC and MNLC. Both MGLC and MNLC had greater pH buffering capacity and were less affected by changes in ionic strength. Competing anions (carbonate and dihydric phosphate) had a larger impact on As(V) removal by MNLC than by MGLC. Adsorption on MNLC reached equilibrium at 60 min, while adsorption on MGLC reached equilibrium at 120 min. The Langmuir adsorption isotherm was a good fit for the experimental data of As(V) adsorption on MGLC and MNLC, and the adsorption kinetics for both followed the pseudo-second-order rate equation. MGLC and MNLC had a larger removal capacity for As(V) than the cenospheres. Compared with MNLC, MGLC is a better absorbent.