Focused ultrasound-mediated small-molecule delivery to potentiate immune checkpoint blockade in solid tumors.

In the last decade, immune checkpoint blockade (ICB) has revolutionized the standard of treatment for solid tumors. Despite success in several immunogenic tumor types evidenced by improved survival, ICB remains largely unresponsive, especially in "cold tumors" with poor lymphocyte infiltration. In addition, side effects such as immune-related adverse events (irAEs) are also obstacles for the clinical translation of ICB. Recent studies have shown that focused ultrasound (FUS), a non-invasive technology proven to be effective and safe for tumor treatment in clinical settings, could boost the therapeutic effect of ICB while alleviating the potential side effects. Most importantly, the application of FUS to ultrasound-sensitive small particles, such as microbubbles (MBs) or nanoparticles (NPs), allows for precise delivery and release of genetic materials, catalysts and chemotherapeutic agents to tumor sites, thus enhancing the anti-tumor effects of ICB while minimizing toxicity. In this review, we provide an updated overview of the progress made in recent years concerning ICB therapy assisted by FUS-controlled small-molecule delivery systems. We highlight the value of different FUS-augmented small-molecules delivery systems to ICB and describe the synergetic effects and underlying mechanisms of these combination strategies. Furthermore, we discuss the limitations of the current strategies and the possible ways that FUS-mediated small-molecule delivery systems could boost novel personalized ICB treatments for solid tumors.

Numerical Simulation on the Effect of Burner Bias Angles on the Performance of a Two-Stage Entrained-Flow Gasifier.

A 2000 t/day HNCERI (Huaneng Clean Energy Research Institute) entrained-flow pulverized coal gasifier suffers from the problem of a high ash-slag ratio. An appropriate bias angle of the burners is the key to solve this issue for the gasifier with a specific structure. A random pore model considering bulk and pore diffusion effects was extended by user-defined function to describe the gasification reactions. The simulation of the gas flow and char gasification characteristics under different bias angles (0, 1.5, 2.5, 3.5, and 4.5°) of the four burners in the first stage was conducted. The simulation results showed favorable agreement with the industrial data. The evaporation, devolatilization, and char oxidation mainly occurred in the first-stage jet zone, and the upflow and downflow zones are dominated by the gasification reactions. The bias angles of the burners mainly affect the scale of gasification reaction zones. As the bias angles increased from 0 to 4.5°, the gas temperature at the slag tap hole decreased from 1880 to 1500 K. The carbon conversion efficiency of the first stage decreases and that of the second stage increases with the bias angle increasing. An optimal bias angle of 2.5° is recommended for the HNCERI gasifier with a total carbon conversion efficiency of 98.16%.

Effect of thermal expansion additives on alleviating the ash deposition of high-sodium coal.

The high content of sodium in coal ash can induce severe ash deposit problems on heated surface. Vermiculite has been investigated to solve this problem in drop-tube furnace recently. In this work, the effects of vermiculite and perlite on appearances, inorganic mineral transformation, elemental composition change and Na capture efficiency of ash deposit were investigated. The results show that the molten deposit obtained by drop-tube furnace at 1373 K was transformed into weakly-condensed deposit and strongly-sticky deposit respectively when vermiculite and perlite were added separately. Vermiculite has a better effect on improving the ash deposition than perlite. The mechanism of alleviating the ash deposition by vermiculite and perlite is proposed as follows: (1) The interaction between ash particles is inhibited due to the combination reactions of thermal expansion additive particles with coal ash particles. (2) The coal ash particles attach to the surface and the gap of thermal expansion additive particles, forming a porous structure. (3) With vermiculite added, Mg2SiO4 (forsterite) increases the fusion point of ash deposit. NaCa2Mg4Al(Si6Al2)O22(OH)2 (pargasite) and Mg1.8Fe0.2SiO4 (forsterite ferroan) result in the weak viscosity of ash deposit. (4) With perlite added, silicate and sodium aluminosilicate in perlite react with coal ash to produce a large amount of amorphous substance, which can flow downwards to make the bottom deposit molten and lead to the strong viscosity of total deposit. (5) Vermiculite has a strong capacity for Na capture at 1023 K, and perlite has a strong capacity for Na capture at 1373 K.