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Background: For patients with locally advanced head and neck squamous cell carcinoma (HNSCC), combined programmed death receptor-1 inhibitor and chemotherapy improved response rate to neoadjuvant therapy. However, treatment response varies among patients. There is no tool to predict pathologic complete response (pCR) with high accuracy for now. To develop a tool based on radiomics features of MRI to predict pCR to neoadjuvant chemoimmunotherapy (NACI) may provide valuable assistance in treatment regimen determination for HNSCC., Methods: From January 2021 to April 2024, a total of 172 patients with HNSCC from three medical center, who received NACI followed by surgery, were included and allocated into a training set (n=84), an internal validation set (n=37) and an external validation set (n=51). Radiomics features were extracted from intratumoral and different peritumoral areas, and radiomics signature (Rad-score) for each area was constructed. A radiomics-clinical nomogram was developed based on Rad-scores and clinicopathological characteristics, tested in the validation sets, and compared with clinical nomogram and combined positive score (CPS) in predicting pCR., Results: The radiomics-clinical nomogram, incorporating peritumoral Rad-score, intratumoral Rad-score and CPS, achieved the highest accuracy with areas under the receiver operating characteristic curve of 0.904 (95% CI, 0.835 to 0.972) in the training cohort, 0.860 (95% CI, 0.722 to 0.998) in the internal validation cohort, and 0.849 (95% CI, 0.739 to 0.959) in the external validation cohort, respectively, which outperformed the clinical nomogram and CPS in predict pCR to NACI for HNSCC., Conclusion: A nomogram developed based on intratumoral and peritumoral MRI radiomics features outperformed CPS, a widely employed biomarker, in predict pCR to NACI for HNSCC, which would provide incremental value in treatment regimen determination., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A peculiar physiological characteristic of the Chinese brown frog (Rana dybowskii) is that its oviduct dilates during pre-brumation rather than during the breeding season. This research aimed to examine the expression of genes connected with lipid synthesis and metabolism in the oviduct of R. dybowskii during both the breeding season and pre-brumation. We observed significant changes in the weight and size of the oviduct between the breeding season and pre-brumation. Furthermore, compared to the breeding season, pre-brumation exhibited significantly lower triglyceride content and a marked increase in free fatty acid content. Immunohistochemical results revealed the spatial distribution of triglyceride synthase (Dgat1), triglyceride hydrolase (Lpl and Hsl), fatty acid synthase (Fasn), and fatty acid oxidases (Cpt1a, Acadl, and Hadh) in oviductal glandular cells and epithelial cells during both the breeding season and pre-brumation. While the mRNA levels of triglycerides and free fatty acid synthesis genes (dgat1 and fasn) did not show a significant difference between the breeding season and pre-brumation, the mRNA levels of genes involved in triglycerides and free fatty acid metabolism (lpl, cpt1a, acadl, acox and hadh) were considerably higher during pre-brumation. Furthermore, the R. dybowskii oviduct's transcriptomic and metabolomic data confirmed differential expression of genes and metabolites enriched in lipid metabolism signaling pathways during both the breeding season and pre-brumation. Overall, these results suggest that alterations in lipid synthesis and metabolism during pre-brumation may potentially influence the expanding size of the oviduct, contributing to the successful overwintering of R. dybowskii.

The oviduct of the Chinese brown frog ( Rana dybowskii ) expands in prehibernation rather than in prespawning, which is one of the physiological phenomena that occur in the preparation for hibernation. Steroid hormones are known to regulate oviductal development. Cholesterol synthesis and steroidogenesis may play an important role in the expansion of the oviduct before hibernation. In this study, we investigated the expression patterns of the markers that are involved in the de novo steroid synthesis pathway in the oviduct of R. dybowskii during prespawning and prehibernation. According to histological analysis, the oviduct of R. dybowskii contains epithelial cells, glandular cells, and tubule lumens. During prehibernation, oviductal pipe diameter and weight were significantly larger than during prespawning. 3-Hydroxy-3-methylglutaryl CoA reductase (HMGCR), low-density lipoprotein receptor (LDLR), steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and steroidogenic factor 1 (SF-1) were detected in epithelial cells in prehibernation and glandular cells during prespawning. HMGCR, LDLR, StAR, and P450scc protein expression levels were higher in prehibernation than during prespawning, but the SF-1 protein expression level did not significantly differ. HMGCR, LDLR, StAR, P450scc ( CYP11A1 ), and SF-1 ( NR5A1 ) mRNA expression levels were significantly higher in prehibernation compared with prespawning. The transcriptome results showed that the steroid synthesis pathway was highly expressed during prehibernation. Existing results indicate that the oviduct is able to synthesize steroid hormones using cholesterol, and that steroid hormones may affect the oviductal functions of R. dybowskii.

Prolactin (PRL) is a hormone crucial for normal reproduction, functioning as an autocrine, paracrine, and endocrine factor. This study aimed to examine the immunolocalization and expression patterns of PRL, prolactin receptor (PRLR), and signal transducer and activator of transcription 5 (STAT5) in the ovaries of wild ground squirrels during both breeding and non-breeding periods. Significant seasonal variations were observed in ovarian weights, with higher values during the breeding season and relatively lower values during the nonbreeding season. PRL, PRLR, STAT5, and p-STAT5 were immunolocalized in granulosa cells and luteal cells during the breeding season, whereas they were exclusively found in granulosa cells during the non-breeding season. The mRNA expression levels of Prl, Prlr, and Stat5 were increased in ovarian tissues during the breeding season compared to the non-breeding season. Moreover, the mean mRNA levels of Prl, Prlr, and Stat5 exhibited a positive correlation with ovarian weights. Both circulating PRL and ovarian PRL concentrations were significantly elevated during the breeding season. Additionally, transcriptomic analysis of ovarian tissues revealed differentially expressed genes possibly associated with ovarian function and mammary gland development, including ovarian follicle development, steroid synthesis, and regulation of reproductive process. These findings suggest that PRL might play an essential endocrine, autocrine, or paracrine role in the regulation of seasonal changes in the ovarian functions in wild ground squirrels.

Prostaglandins (PGs) serve as signaling molecules that regulate various physiological processes, including inflammation, immune response, blood clotting, and reproduction. The aim of this study was to investigate the immunolocalizations and expression patterns of prostaglandin-E2 (PGE2), cyclooxygenase (COX)-1, and COX-2, as well as its receptor subtypes 4 (EP4) in the scent glands of muskrats ( Ondatra zibethicus ) during the breeding and nonbreeding periods. There were significant seasonal differences in the scent glandular mass, with higher values in the breeding season and relatively low in the nonbreeding season. PGE2, EP4, COX-1, and COX-2 have been immunolocalized in the scent glandular and epithelial cells in both breeding and nonbreeding seasons, whereas no immunostaining was observed in the interstitial cells. The protein and mRNA expression levels of EP4, COX-1, and COX-2 were higher in the scent glands of the breeding season than those of the nonbreeding season. The mean mRNA levels of EP4, COX-1, and COX-2 were positively correlated with the scent glandular weights. The circulating follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), and PGE2, as well as scent glandular PGE2 and dihydrotestosterone (DHT) concentrations, were also significantly higher in the breeding season. In addition, the transcriptomic study in the scent glands identified that differentially expressed genes might be related to fatty carboxylic monocarboxylic acid, steroidogenic-related pathways, and prostanoid metabolic processes. These findings suggested that prostaglandin-E2 might play an essential autocrine or paracrine role in regulating seasonal changes in the scent glandular functions of the muskrats.

As a vital male accessory reproductive gonad, the prostate requires vascular endothelial growth factors for promoting its growth and development. In this study, we investigated the localizations and expressions of vascular endothelial growth factor (VEGF) and its receptors including VEGF-receptor1 (VEFGR1) and VEGF-receptor2 (VEGFR2) in the prostate of the wild ground squirrels during the breeding and the non-breeding seasons. The values of total prostate weight and volume in the breeding season were higher than those in the non-breeding season. Histological observations showed that the exocrine lumens of the prostate expanded in the breeding season and contracted in the non-breeding season. The mRNA expression levels of VEGF and VEGFR2 in the prostate were higher in the breeding season than those in the non-breeding season, but the mRNA expression level of VEGFR1 had no significant change between the breeding and non-breeding seasons. Immunohistochemical results revealed that VEGF, VEGFR1 and VEGFR2 were presented in epithelial and stromal cells during the breeding and non-breeding seasons. In addition, the microvessels of the prostate were widely distributed and the number of microvessels increased obviously in the breeding season, while decreased sharply in the non-breeding season. These results suggested that expression levels of VEGF and VEGFR2 might be correlated with seasonal changes in morphology and functions of the prostate, and VEGF might serve as pivotal regulators to affect seasonal changes in the prostate functions of the wild male ground squirrels via an autocrine/paracrine pathway.