Immunotherapy aiming to rescue or boost antitumor immunity is an emerging strategy for treatment of cancers. The efficacy of immunotherapy is strongly controlled by the immunological milieu of cancer patients. Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature myeloid cell populations with immunosuppressive functions accumulating in individuals during tumor progression. The signaling mechanisms of MDSC activation have been well studied. However, there is little known about the metabolic status of MDSCs and the physiological role of their metabolic reprogramming. In this study, we discovered that myeloid cells upregulated their glycolytic genes when encountered with tumor-derived factors. MDSCs exhibited higher glycolytic rate than their normal cell compartment did, which contributed to the accumulation of the MDSCs in tumor-bearing hosts. Upregulation of glycolysis prevented excess reactive oxygen species (ROS) production by MDSCs, which protected MDSCs from apoptosis. Most importantly, we identified the glycolytic metabolite, phosphoenolpyruvate (PEP), as a vital antioxidant agent able to prevent excess ROS production and therefore contributed to the survival of MDSCs. These findings suggest that glycolytic metabolites have important roles in the modulation of fitness of MDSCs and could be potential targets for anti-MDSC strategy. Targeting MDSCs with analogs of specific glycolytic metabolites, for example, 2-phosphoglycerate or PEP may diminish the accumulation of MDSCs and reverse the immunosuppressive milieu in tumor-bearing individuals.
This study reports a two-step method to synthesize spermidine-capped fluorescent carbon quantum dots (Spd-CQDs) and their potential application as an antibacterial agent. Fluorescent carbon quantum dots (CQDs) are synthesized by pyrolysis of ammonium citrate in the solid state and then modified with spermidine by a simple heating treatment without a coupling agent. Spermidine, a naturally occurring polyamine, binds with DNA, lipids, and proteins involved in many important processes within organisms such as DNA stability, and cell growth, proliferation, and death. The antimicrobial activity of the as-synthesized Spd-CQDs (size ≈4.6 nm) has been tested against non-multidrug-resistant E. coli, S. aureus, B. subtilis, and P. aeruginosa bacteria and also multidrug-resistant bacteria, methicillin-resistant S. aureus (MRSA). The minimal inhibitory concentration value of Spd-CQDs is much lower (>25 000-fold) than that of spermidine, indicating their promising antibacterial characteristics. The mechanism of antibacterial activity is investigated, and the results indicate that Spd-CQDs cause significant damage to the bacterial membrane. In vitro cytotoxicity and hemolysis analyses reveal the high biocompatibility of Spd-CQDs. To demonstrate its practical application, in vitro MRSA-infected wound healing studies in rats have been conducted, which show faster healing, better epithelialization, and formation of collagen fibers when Spd-CQDs are used as a dressing material.
Abstract-In this paper, a design of new tri-band bandpass filter for the application of GSM (1.8 GHz), WiMAX (2.7 GHz) and UWB (3.3-4.8 GHz) is proposed. The first two narrow passbands are created, and the bandwidth of the third passband can be tuned by properly selecting the impedance ratio (R) and physical length ratio (u) of the asymmetric stepped-impedance resonator. To improve passband performance and form the UWB passband, a U-shape defected ground structure and extra extended coupling lines are integrated with the asymmetric SIR. Due to the three transmission zeros appearing near the passband edges, the band selectivity of the proposed filter is much improved. The filter was fabricated, and the measured results have a good agreement with the full-wave simulated ones.
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