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Pyrolytic synergistic interactions, in which the production of pyrolyzates is enhanced or inhibited, commonly occur during the co-pyrolysis of different polymeric materials, such as plastics and biomass. Although these interactions can increase the yield of desired pyrolysis products under controlled degradation conditions, the desired compounds must be separated from complex pyrolyzates and further purified. To balance these dual effects, this study was aimed at examining pyrolytic synergistic interactions during slow heating co-pyrolysis of biodegradable plastics including polylactic acid (PLA) and poly(3-hydroxybutyrate-co-3-hydroxyhexaoate) (PHBH) and petroleum-based plastics including high-density polyethylene (HDPE), polypropylene (PP), and polystyrene (PS). Comprehensive investigations based on thermogravimetric analysis, pyrolysis–gas chromatography/mass spectrometry, and evolved gas analysis-mass spectrometry revealed that PLA and PHBH decompose at lower temperatures (273–378 °C) than HDPE, PP, and PS (386–499 °C), with each polymer undergoing independent decomposition without any pyrolytic interactions. Thus, the independent pyrolysis of biodegradable plastics, such as PLA and PHBH, with common plastics, such as HDPE, PP, and PS, can theoretically be realized through temperature control, enabling the selective recovery of their pyrolyzates in different temperature ranges. Thus, pyrolytic approaches can facilitate the treatment of mixed biodegradable and common plastics. [ABSTRACT FROM AUTHOR]

The CLIP1-LTK fusion was recently discovered as a novel oncogenic driver in non-small cell lung cancer (NSCLC). Lorlatinib, a third-generation ALK inhibitor, exhibited a dramatic clinical response in a NSCLC patient harboring CLIP1-LTK fusion. However, it is expected that acquired resistance will inevitably develop, particularly by LTK mutations, as observed in NSCLC induced by oncogenic tyrosine kinases treated with corresponding tyrosine kinase inhibitors (TKIs). In this study, we evaluate eight LTK mutations corresponding to ALK mutations that lead to on-target resistance to lorlatinib. All LTK mutations show resistance to lorlatinib with the L650F mutation being the highest. In vitro and in vivo analyses demonstrate that gilteritinib can overcome the L650F-mediated resistance to lorlatinib. In silico analysis suggests that introduction of the L650F mutation may attenuate lorlatinib-LTK binding. Our study provides preclinical evaluations of potential on-target resistance mutations to lorlatinib, and a novel strategy to overcome the resistance. A novel strategy using gilteritinib can overcome resistance to lorlatinib in non-small cell lung cancer with CLIP1-LTK-L650F mutation. [ABSTRACT FROM AUTHOR]

Cancer cells employ glycolysis for their survival and growth (the "Warburg effect"). Consequently, surrounding cells including immune cells in the tumor microenvironment (TME) are exposed to hypoglycemic, hypoxic, and low pH circumstances. Since effector T cells depend on the glycolysis for their survival and functions, the metabolically harsh TME established by cancer cells is unfavorable, resulting in the impairment of effective antitumor immune responses. By contrast, immunosuppressive cells such as regulatory T (Treg) cells can infiltrate, proliferate, survive, and exert immunosuppressive functions in the metabolically harsh TME, indicating the different metabolic dependance between effector T cells and Treg cells. Indeed, some metabolites that are harmful for effector T cells can be utilized by Treg cells; lactic acid, a harmful metabolite for effector T cells, is available for Treg cell proliferation and functions. Deficiency of amino acids such as tryptophan and glutamine in the TME impairs effector T cell activation but increases Treg cell populations. Furthermore, hypoxia upregulates fatty acid oxidation via hypoxia-inducible factor 1α (HIF-1α) and promotes Treg cell migration. Adenosine is induced by the ectonucleotidases CD39 and CD73, which are strongly induced by HIF-1α, and reportedly accelerates Treg cell development by upregulating Foxp3 expression in T cells via A2AR-mediated signals. Therefore, this review focuses on the current views of the unique metabolism of Treg cells dictated by cancer cells. In addition, potential cancer combination therapies with immunotherapy and metabolic molecularly targeted reagents that modulate Treg cells in the TME are discussed to develop "immune metabolism-based precision medicine". [ABSTRACT FROM AUTHOR]