Nanotherapeutics targeting autophagy regulation for improved cancer therapy.

The clinical efficacy of current cancer therapies falls short, and there is a pressing demand to integrate new targets with conventional therapies. Autophagy, a highly conserved self-degradation process, has received considerable attention as an emerging therapeutic target for cancer. With the rapid development of nanomedicine, nanomaterials have been widely utilized in cancer therapy due to their unrivaled delivery performance. Hence, considering the potential benefits of integrating autophagy and nanotechnology in cancer therapy, we outline the latest advances in autophagy-based nanotherapeutics. Based on a brief background related to autophagy and nanotherapeutics and their impact on tumor progression, the feasibility of autophagy-based nanotherapeutics for cancer treatment is demonstrated. Further, emerging nanotherapeutics developed to modulate autophagy are reviewed from the perspective of cell signaling pathways, including modulation of the mammalian target of rapamycin (mTOR) pathway, autophagy-related (ATG) and its complex expression, reactive oxygen species (ROS) and mitophagy, interference with autophagosome-lysosome fusion, and inhibition of hypoxia-mediated autophagy. In addition, combination therapies in which nano-autophagy modulation is combined with chemotherapy, phototherapy, and immunotherapy are also described. Finally, the prospects and challenges of autophagy-based nanotherapeutics for efficient cancer treatment are envisioned.

Nanomaterial-mediated modulation of the cGAS-STING signaling pathway for enhanced cancer immunotherapy.

Despite the current promise of immunotherapy, many cancer patients still suffer from challenges such as poor immune response rates, resulting in unsatisfactory clinical efficacy of existing therapies. There is an urgent need to combine emerging biomedical discoveries and innovations in traditional therapies. Modulation of the cGAS-STING signalling pathway represents an important innate immunotherapy pathway that serves as a crucial DNA sensing mechanism in innate immunity and viral defense. It has attracted increasing attention as an emerging target for cancer therapy. The recent advancements in nanotechnology have led to the significant utilization of nanomaterials in cancer immunotherapy, owing to their exceptional physicochemical properties such as large specific surface area and efficient permeability. Given the rapid development of cancer immunotherapy driven by the cGAS-STING activation, this study reviews the latest research progress in employing nanomaterials to modulate this signaling pathway. Based on the introduction of the main activation mechanisms of cGAS-STING pathway, this review focuses on nanomaterials that mediate the agonists involved and effectively activate this signaling pathway. In addition, combination nanotherapeutics based on the activation of the cGAS-STING signaling pathway are also discussed, including emerging strategies combining nanoformulated agonists with chemotherapy, radiotherapy as well as other immunomodulation in tumor targeting therapy. STATEMENT OF SIGNIFICANCE: Given the rapid development of cancer immunotherapy driven by the cGAS / STING activation, this study reviews the latest research advances in the use of nanomaterials to modulate this signaling pathway. Based on the introduction of key cGAS-STING components and their activation mechanisms, this review focuses on nanomaterials that can mediate the corresponding agonists and effectively activate this signaling pathway. In addition, combination nanotherapies based on the activation of the cGAS-STING signaling pathway are also discussed, including emerging strategies combining nanoformulated agonists with chemotherapy, radiotherapy as well as immunomodulation in cancer therapy,.

Summary of Turbocharging as a Waste Heat Recovery System for a Variable Altitude Internal Combustion Engine.

The increase in altitude causes the decrease in internal combustion engine power and the increase in pollutant emission. Converting waste heat into more useful forms of energy through the recovery of waste heat from internal combustion engines is the most promising mechanism for improving both of these goals. This paper comprehensively reviews the development and research of waste heat recovery technology of an internal combustion engine in a variable altitude environment. It is found that exhaust gas turbocharging is the most promising waste heat recovery technology to restore high-altitude internal combustion engine power. Turbochargers are affected by low temperature and low pressure at high altitudes, resulting in poor environmental adaptability, inadequate supercharging ratios, and decreased supercharging efficiency. Therefore, it is very important to select the high pressurization system facing the plateau area and its reasonable matching characteristics. The quality of exhaust energy determines how much waste heat a turbine can recover, and only the exergy part of exhaust energy can realize heat/work conversion. The main disadvantage of turbocharging technology applied in the plateau area is that the speed ratio deviates from the design value, leading to the increase of flow loss inside the supercharger. Therefore, optimizing the internal flow field of a high-altitude supercharger is a key problem to improve the efficiency of energy recovery. The conclusion drawn from this Review is that a two-stage turbocharging system will be a key technology to improve the thermal efficiency and reduce the fuel consumption of high-altitude internal combustion engines in the coming decades. In addition, the efficient utilization of the exhaust energy of the two-stage turbine and the influence of the variable compression process of the two-stage compressor on the working medium in the cylinder will be the focus of future research.