Search

Abstract We report the first case of drug‐induced interstitial lung disease attributed to lemborexant. A 66‐year‐old man reported to our hospital with the acute onset of cough and breathlessness with ground‐glass opacity on radiological examination. Symptoms were identified after taking lemborexant for 2 consecutive days. The patient had undergone lemborexant treatment 2 years prior and had exhibited no symptoms at that time. The drug‐induced lymphocyte stimulation test for lemborexant was positive. He showed rapid improvement upon treatment with steroid. With the rise in prescriptions of lemborexant for insomnia, lemborexant should be considered as a possible cause of drug‐induced interstitial lung disease.

Following the Fukushima Daiichi Nuclear Power Plant accident in 2011, most of the released 137Cs remained in the litter and surface soil of the adjacent forest floor. However, 137Cs absorption by large soil invertebrates near this site has not been estimated. The aim of this study was to understand the role of soil macroinvertebrates in 137Cs uptake from forest litter into forest ecosystems. Breeding experiments were conducted using scarab beetle larvae (Protaetia orientalis). Dissection experiments revealed that 85% of the total 137Cs was concentrated in the digestive tract of larvae, while a low proportion was absorbed into the skin and muscle tissues. The 137Cs absorption rate, indicating the transfer of 137Cs from consumed litter to larval tissue, was low (0.39%). 137Cs concentrations decreased to one-fourth from larva to imago, possibly due to excretion from the digestive tract and during eclosion. In the elimination experiment, biological half-lives were 0.26-0.64 and 0.11-0.47 days and 3.35-48.30 and 4.01-17.70 days for the digestive tract and muscle/skin tissues in the fast and slow components, respectively, corresponding to 137Cs discharge from the gastrointestinal tract and physiological clearance. In the sequential extraction experiment, litter digestion by flower chafer larvae significantly reduced the bioavailable fraction of 137Cs including water-soluble, exchangeable, oxidized, and organic forms, from 23.2% in litter to 17.7% in feces. Residual 137Cs was not reduced by digestion, probably because it was fixed in soil clay. Our study on breeding experiments of the Scarabaeidae beetle confirmed the low bioavailability of 137Cs in the litter in Fukushima. However, litter feeders may play an important role in transferring 137Cs to higher trophic levels in the forest ecosystem by extracting the bioavailable fraction of the vast stock of 137Cs on the forest floor.

IntroductionProgrammed cell death–ligand 1 (PD-L1) is a biomarker for prediction of the clinical efficacy of immune checkpoint inhibitors in various cancer types. The role of cytokines in regulation of PD-L1 expression in tumor cells has not been fully characterized, however. Here we show that interleukin-1β (IL-1β) plays a key role in regulation of PD-L1 expression in non–small cell lung cancer (NSCLC).MethodsWe performed comprehensive screening of cytokine gene expression in NSCLC tissue using available single-cell RNA-Sequence data. Then we examined the role of IL-1β in vitro to elucidate its induction of PD-L1 on NSCLC cells.ResultsThe IL-1β gene is highly expressed in the tumor microenvironment, particularly in macrophages. The combination of IL-1β and interferon-γ (IFN-γ) induced a synergistic increase in PD-L1 expression in NSCLC cell lines. IL-1β and IFN-γ also cooperatively activated mitogen-activated protein kinase (MAPK) signaling and promoted the binding of downstream transcription factors to the PD-L1 gene promoter. Furthermore, inhibitors of MAPK signaling blocked upregulation of PD-L1 by IL-1β and IFN-γ.DiscussionOur study reports high levels of IL-1β in the tumor microenvironment may cooperate with IFN-γ to induce maximal PD-L1 expression in tumor cells via activation of MAPK signaling, with the IL-1β–MAPK axis being a promising therapeutic target for attenuation of PD-L1–mediated suppression of antitumor immunity.

After the Tokyo Electric Power Company Fukushima Daiichi Nuclear Power Plant accident in Japan, freshwater ecosystems near the site remained contaminated by radiocesium (RCs). Clarifying RCs concentrations in aquatic insects is crucial because fishes consume these insects that transfer RCs into freshwater ecosystems. As aquatic insects are usually measured for radioactivity in bulk samples of several tens of insects, variation in RCs concentration among individuals is not captured. In this study, we investigated the variability in 137Cs activity concentration in individual aquatic insects in detritivorous caddisfly (Stenopsyche marmorata) and carnivorous dobsonfly (Protohermes grandis) larvae from the Ota River, Fukushima. Caddisfly larvae showed sporadically higher radioactivity in 4 of the 46 caddisfly larvae, whereas no such outliers were observed in 45 dobsonfly larvae. Autoradiography and scanning electron microscopy analyses confirmed that these caddisfly larvae samples contained radiocesium-bearing microparticles (CsMPs), which are insoluble Cs-bearing silicate glass particles. CsMPs were also found in potential food sources of caddisfly larvae, such as periphyton and drifting particulate organic matter, indicating that larvae may ingest CsMPs along with food particles of similar size. Although CsMP distribution and uptake by organisms in freshwater ecosystems is relatively unknown, our study demonstrates that CsMPs can be taken up by aquatic insects.