Chronic hepatitis B virus (HBV) infection is associated with functionally impaired virus-specific T cell responses. Although the myeloid-derived suppressor cells (MDSCs) are known to play a critical role in impairing antiviral T cell responses, viral factors responsible for the expansion of MDSCs in chronic hepatitis B (CHB) remain obscure. In order to elucidate the mechanism of monocytic MDSCs (mMDSCs) expansion and T cell function suppression during persistent HBV infection, we analyzed the circulation frequency of mMDSCs in 164 CHB patients and 70 healthy donors, and found that the proportion of mMDSCs in HBeAg (+) CHB patients was significantly increased compared to that in HBeAg (-) patients, which positively correlated with the level of HBeAg. Furthermore, exposure of peripheral blood mononuclear cells (PBMCs) isolated from healthy donors to HBeAg led to mMDSCs expansion and significant upregulation of IL-1β, IL-6 and indoleamine-2, 3-dioxygenase (IDO), and depletion of the cytokines abrogated HBeAg-induced mMDSCs expansion. Moreover, HBeAg-induced mMDSCs suppressed the autologous T-cell proliferation in vitro , and the purified mMDSCs from HBeAg (+) subjects markedly reduced the proliferation of CD4 + and CD8 + T cells and IFN-γ production, which could be efficiently restored by inhibiting IDO. In summary, HBeAg-induced mMDSCs expansion impairs T cell function through IDO pathway and favors the establishment of a persistent HBV infection, suggesting a mechanism behind the development of HBeAg-induced immune tolerance.

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An HBsAg-HBIG therapeutic vaccine (Yeast-derived Immune Complexes, YIC) for chronic hepatitis B (CHB) patients has undergone a series of clinical trials. The HBeAg sero-conversion rate of YIC varied from 21.9% to 14% depending on the immunization protocols from 6 to 12 injections. To analyze the immunological mechanisms exerted by 6 injections of YIC, 44 CHB patients were separately immunized with YIC, alum as adjuvant control or normal saline as blank control, with add on of antiviral drug Adefovir in all groups. Kinetic increase in Th1 and Th2 cells CD4 T cell sub-populations with association in decrease in Treg cells and increase of Tc1 and Tc17 cells in CD8 T cells were observed in YIC immunized group. No such changes were found in the other groups. By multifunctional analysis of cytokine profiles, significant increase of IL-2 levels was observed, both in CD4 and CD8 T cells in the YIC immunized group, accompanied by increase in IFN-gamma and decrease of inhibitory factors (IL-10, TGF-β and Foxp3) in CD4 T cells. In the alum immunized group, slight increase of IL-10, TGF-β and Foxp3 in CD4 T cells was found after the second injection, but decreased after more injections, suggesting that alum induced early inflammatory responses to a certain extent. Similar patterns of responses of IL-17A and TNF-α in CD8T cells were shown between YIC and the saline group. Results indicate that add on of Adefovir, did not affect host specific immune responses.

The steam gasification of Shengli lignite (SL-raw) and demineralized samples (SL-HCl and SL-HF) obtained by sequential leaching with hydrochloric acid and hydrofluoric acid aqueous solutions was conducted using fixed-bed microreactor equipment. The high steam gasification rate of Shengli lignite was achieved at a lower temperature range of 616−750°C compared to the demineralized lignite SL-HCl and SL-HF, indicating that the inherent minerals within Shengli lignite had a distinguished catalytic effect on the steam gasification. The initiating temperature for the steam gasification of SL-raw was 616°C, which was about 140°C lower compared to the initiating temperature of demineralized lignite samples SL-HCl and SL-HF at 756°C. On the basis of the very similar characteristics of steam gasification of SL-HCl and SL-HF, it was indeed confirmed that the principal component of inherent minerals that played a catalytic effect on the steam gasification reaction was calcium ion, which can be readily eluted by hydrochloric acid aqueous solution. The natural minerals within SL-raw not only effectively accelerated the reactivity of steam gasification but also significantly enhanced the H 2 production and substantially reduced the formation of CO, especially in the low-temperature range from 616 to 750°C. The optimal performances of steam gasification of Shengli lignite at lower temperatures were majorly attributed to the significant improvement of the water-gas shift (WGS) reaction by the inherent minerals. This study demonstrated that Shengli lignite could be a potential feedstock for the production of H 2 -rich synthesis gas by the steam gasification at the temperatures below 750°C.

The global spread of the novel coronavirus SARS-CoV-2 urgently requires discovery of effective therapeutics for the treatment of COVID-19. The spike (S) protein of SARS-CoV-2 plays a key role in receptor recognition, virus-cell membrane fusion and virus entry. Our previous studies have reported that 3-hydroxyphthalic anhydride-modified chicken ovalbumin (HP-OVA) serves as a viral entry inhibitor to prevent several kinds of virus infection. Here, our results reveal that HP-OVA can effectively inhibit SARS-CoV-2 replication and S protein-mediated cell-cell fusion in a dose-dependent manner without obvious cytopathic effects. Further analysis suggests that HP-OVA can bind to both the S protein of SARS-CoV-2 and host angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV-2, and disrupt the S protein-ACE2 interaction, thereby exhibiting inhibitory activity against SARS-CoV-2 infection. In summary, our findings suggest that HP-OVA can serve as a potential therapeutic agent for the treatment of deadly COVID-19.