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Immune checkpoint inhibitors provide a definite survival benefit for patients with driver‐negative advanced non‐small cell lung cancer (NSCLC), but predictors of efficacy are still lacking. There may be a relationship between immune inflammatory state and tumor immune response. We explored the relationship of serum neutrophil extracellular traps (NETs) with infiltrating cells in the tumor tissues of patients with NSCLC as well as their relationship with the therapeutic efficacy of programmed cell death protein 1 (PD‐1) inhibitors. Serum myeloperoxidase (MPO)‐double‐stranded DNA (dsDNA) was detected as a marker of NET serum concentration. T cells were detected by immunohistochemical staining, and neutrophils were counted by MPO immunofluorescence staining. Of the 31 patients with NSCLC, a longer progression‐free survival after PD‐1 inhibitor treatment was associated with higher levels of CD3+ T cells, a lower neutrophil : CD3+‐T‐cell ratio (NEU/CD3+) and lower neutrophil : CD8+‐T‐cell ratio (NEU/CD8+) in tumor tissues. Patients with higher serum NETs were more likely to develop progressive disease after treatment (P = 0.003) and to have immune‐related adverse events (IrAEs) as well as higher NEU/CD3+ and NEU/CD8+. The combined model of serum NETs, CD8+ T cells, and tumor proportion score (TPS) significantly improved the prediction of PD‐1 inhibitor efficacy [P = 0.033; area under the curve (AUC) = 0.881]. Our results indicate that serum NETs are effective predictors of PD‐1 inhibitor response and reflect the tissue neutrophil‐to‐lymphocyte ratio and IrAE levels. The combined model of serum NETs, CD8+ T cells, and TPS is a powerful tool for predicting the efficacy of PD‐1 inhibitor treatment in patients with NSCLC. [ABSTRACT FROM AUTHOR]

Natural and synthetic environmental estrogens (EEs) are widespread and have received extensive attention. Our previous studies demonstrated that depletion of the cytochrome P450 17a1 gene (cyp17a1) leads to all‐testis differentiation phenotype in zebrafish and common carp. In the present study, cyp17a1‐deficient zebrafish with defective estrogen biosynthesis were used for the evaluation of EEs, as assessed by monitoring vitellogenin (vtg) expression. A rapid and sensitive assessment procedure was established with the 3‐day administration of estradiol (E2), followed by examination of the transcriptional expression of vtgs in our cyp17a1‐deficient fish. Compared with the control fish, a higher E2‐mediated vtg upregulation observed in cyp17a1‐deficient zebrafish exposed to 0.1 μg/L E2 is known to be estrogen receptor–dependent and likely due to impaired in vivo estrogen biosynthesis. The more responsive vtg expression in cyp17a1‐deficient zebrafish was observed when exposed to 200 and 2000 μg/L bisphenol A (BPA) and perfluoro‐1‐octanesulfonate (PFOS). The estrogenic potentials of E2, BPA, and PFOS were compared and assessed by the feminization effect on ovarian differentiation in cyp17a1‐deficient zebrafish from 18 to 50 days postfertilization, based on which a higher sensitivity of E2 in ovarian differentiation than BPA and PFOS was concluded. Collectively, through the higher sensitivity to EEs and the capacity to distinguish chemicals with different estrogenic potentials exhibited by the all‐male cyp17a1‐deficient zebrafish with impaired estrogen biosynthesis, we demonstrated that they can be used as an excellent in vivo model for the evaluation of EEs. Environ Toxicol Chem 2024;43:1062–1074. © 2024 SETAC [ABSTRACT FROM AUTHOR]

Simple Summary: Tachykinin1 (tac1) gene products participate in the regulation of hormone secretion in the pituitary of Dabry's sturgeon. Two products of tac1 gene, Substance P (SP) and neurokinin A (NKA), were initially confirmed to regulate the gene expression of two gonadotropins (lh and fsh) in the Dabry's sturgeon pituitary tissue by intraperitoneal injection in vivo and co-culture of primary cells in vitro. This research presents the initial investigation into the reproductive role of SP and NKA in Dabry's sturgeon, offering a valuable insights for advancing efficient ripening techniques in artificial breeding of sturgeon. As an ancient and endangered species unique to the Yangtze River in China, the wild population of the Dabry's sturgeon has become scarce. Due to the long time till the first sexual maturity of Dabry's sturgeon, the population of artificially bred Dabry's sturgeon recovered slowly. As a member of the tachykinin family, TAC1 has been reported to have a variety of functions in mammals such as pain control, smooth muscle contraction and reproductive cycle regulation, but the function of Tac1 in fish has been rarely reported. In this study, we synthesized two tac1 gene products, Substance P (SP) and neurokinin A (NKA), and further verified the effect of two tac1 gene products on the secretion of related hormones in the pituitary of Dabry's Sturgeon by intraperitoneal injection and co-culture of primary cells. Expression studies revealed that the newly cloned tac1 were mainly distributed in the hypothalamus and pituitary tissue of the brain. In prepubertal Dabry's sturgeon, this study showed that the two gonadotropins' mRNA levels in pituitary tissue can be significantly increased by SP and NKA through intraperitoneal injection, and the LH protein level in serum was also increased. Further study showed that both NKA and SP could promote the two gonadotropins' mRNA expression in pituitary cells of Dabry's sturgeon. In addition, we explored the optimal dose and time of SP and NKA on pituitary cells is 24 h and over 10 nM. These results, as a whole, suggested that tac1 gene products play an important role in gonadotropin release and gonadal development in prepubertal Dabry's sturgeon. [ABSTRACT FROM AUTHOR]