Myeloid-derived suppressor cells (MDSCs) are a heterogenic population of immature myeloid cells with immunosuppressive effects, which undergo massive expansion during tumor progression. These cells not only support immune escape directly but also promote tumor invasion via various non-immunological activities. Besides, this group of cells are proved to impair the efficiency of current antitumor strategies such as chemotherapy, radiotherapy, and immunotherapy. Therefore, MDSCs are considered as potential therapeutic targets for cancer therapy. Treatment strategies targeting MDSCs have shown promising outcomes in both preclinical studies and clinical trials when administrated alone, or in combination with other anticancer therapies. In this review, we shed new light on recent advances in the biological characteristics and immunosuppressive functions of MDSCs. We also hope to propose an overview of current MDSCs-targeting therapies so as to provide new ideas for cancer treatment.
In recent years, immunotherapy has showed fantastic promise in pioneering and accelerating the field of cancer therapy and embraces unprecedented breakthroughs in clinical practice. The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (CRISPR-Cas9) system, as a versatile gene-editing technology, lays a robust foundation to efficiently innovate cancer research and cancer therapy. Here, we summarize recent approaches based on CRISPR/Cas9 system for construction of chimeric antigen receptor T (CAR-T) cells and T cell receptor T (TCR-T) cells. Besides, we review the applications of CRISPR/Cas9 in inhibiting immune checkpoint signaling pathways and highlight the feasibility of CRISPR/Cas9 based engineering strategies to screen novel cancer immunotherapy targets. Conclusively, we discuss the perspectives, potential challenges and possible solutions in this vivid growing field.
Elevated levels of total dissolved gas (TDG) may occur downstream of dams during the spill process. These high levels would increase the incidence of gas bubble disease in fish and cause severe environmental impacts. With increasing numbers of cascade hydropower stations being built or planned, the cumulative effects of TDG supersaturation are becoming increasingly prominent. The TDG saturation distribution in the downstream reaches of the Jinsha River was studied to investigate the cumulative effects of TDG supersaturation resulting from the cascade hydropower stations. A comparison of the effects of the joint operation and the single operation of two hydropower stations (XLD and XJB) was performed to analyze the risk degree to fish posed by TDG supersaturation. The results showed that water with supersaturated TDG generated at the upstream cascade can be transported to the downstream power station, leading to cumulative TDG supersaturation effects. Compared with the single operation of XJB, the joint operation of both stations produced a much higher TDG saturation downstream of XJB, especially during the non-flood discharge period. Moreover, the duration of high TDG saturation and the lengths of the lethal and sub-lethal areas were much higher in the joint operation scenario, posing a greater threat to fish and severely damaging the environment. This work provides a scientific basis for strategies to reduce TDG supersaturation to the permissible level and minimize the potential risk of supersaturated TDG.
The total dissolved gas (TDG) supersaturation that results from dam spillage may cause adverse effects, including increases in the risk of gas-bubble disease and mortality in fish. The accurate prediction of TDG levels is necessary in the exploration of measures for ameliorating the effects of TDG supersaturation. Based on an analysis of the mechanisms of hydropower projects with a plunging jet that produces high TDG levels, the process of TDG generation is divided into three stages. In Stage 1, TDG levels return to normal during jet spillage in air; in Stage 2, gas is dissolved in the stilling basin under high pressure; and in Stage 3, the TDG is abruptly released at the outlet of the stilling basin. According to previous research on Stage 1, the TDG level of water entering stilling basins can reach 100%. Experiments were carried out to estimate the TDG levels in Stage 2 under different pressures and retention times, and these experiments indicated that a TDG level above equilibrium saturation (ΔG 0) displays a linear relationship with the average pressure (ΔP) and a negative exponential relationship with retention time (t R). Experiments were also conducted using physical models of the Songta and Yangfanggou dam projects in China to develop a method for estimating the retention time in stilling basins. The resulting formula for estimating the retention time is a function of the water depth in the stilling basin (h k), length of the stilling basin (l), distance between the toe of the dam and impact point of the jet (l 0), and the dimensionless number at the stilling basin outlet λ. For Stage 3, in which the abrupt release of TDG occurs, field measurements were used to determine the values of the parameters used in the abrupt release expression contained in the model. By combining the results for the three stages, a predictive model of TDG levels was obtained. TDG observations collected at six different hydropower projects in China were used for validation. Substantial agreement between predictions and measurements was found. This work may provide a scientific basis for the production of precise predictive models of TDG levels, and it has considerable application value in assessing the effects of TDG and minimizing the risks posed by elevated TDG levels to aquatic life.
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