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Background: As metastatic papillary thyroid carcinoma becomes increasingly challenging to treat, immunotherapy has emerged as a new research direction. Tumor-associated macrophages (TAMs) influence the occurrence, invasion, and metastasis of tumors. Apolipoprotein E (APOE) can regulate the polarization changes of macrophages and participate in the remodeling of the tumor microenvironment. However, the role of APOE in regulating the polarization and biological functions of TAMs in papillary thyroid carcinoma (PTC) remains unclear, as it acts as a dual biomarker. Methods: We probed APOE expression in PTC tissues using immunohistochemical staining. A cell co-culture model was established where different APOE-expressing K1 cells were co-cultured with THP-1-derived M0 macrophages. An in-depth analysis of macrophage polarization behavior was performed using real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting. Subsequently, the impact of APOE-regulated macrophages on tumor cell behavior, especially proliferation, migration, and invasion, was evaluated utilizing IncuCyte ZOOM system, flow cytometry, colony formation, and scratch experiments. Finally, we used a xenograft model to confirm the effects of APOE on PTC tumorigenesis. Results: Tumor dimensions, stage, and lymphatic metastases were significantly associated with increased APOE expression in PTC tissues. K1 cells were markedly limited in their proliferation, migration, and invasion abilities when APOE expression was silenced, a process mediated by the PI3K/Akt/NF-κB signaling axis. Moreover, APOE is a key facilitator of the enhancement of the anti-inflammatory cytokines IL-10 and TGF-β1. In PTC cellular models, APOE contributed to the phenotypic shift of THP-1 derived macrophages towards an M2 phenotypic polarization, predominantly through the modulation of IL-10. Furthermore, in vivo studies involving athymic nude mice have demonstrated pivotal role of APOE in tumor progression and the induction of M2-like TAM polarization. Conclusion: Our results elucidated that APOE could promote the shift of TAMs from M0-type to M2-type polarization by regulating inflammatory factors expressions in K1 cell through the PI3K/Akt/NF-κB pathway. These findings are crucial for understanding the molecular mechanisms underlying PTC pathogenesis and for developing immunological drugs to treat this disease.

Cisplatin (CDDP) stands as a highly effective chemotherapeutic agent; however, its ototoxicity remains a perplexing challenge in the field. Formononetin (FMNT), a potent flavonoid isolated from Astragalus membranaceus, displays a diverse range of promising pharmacological activities, encompassing antioxidant, anti-apoptotic, and anti-inflammatory effects. Nonetheless, the advantageous effects of FMNT on cisplatin-induced cochlear hair cell injury demand further investigation. This study aimed to assess the protective properties of FMNT against cisplatin-induced hair cell damage by conducting in vitro assays on explant-cultured cochlear hair cells. The findings revealed that FMNT exhibited a notable reduction in cisplatin-induced hair cell apoptosis. Also, FMNT effectively mitigated the accumulation of reactive oxygen species and mitochondrial damage in cochlear explants exposed to cisplatin, while also restoring the turnover of the reduced glutathione (GSH)/glutathione disulfide (GSSG) ratio. Furthermore, our study demonstrated that FMNT protects hair cells against CDDP injury through the activation of the PI3K/AKT-Nrf2 signaling pathway. Consequently, formononetin emerges as a potential therapeutic agent for the treatment of cisplatin-induced ototoxicity.

Generally, deciduous and evergreen trees coexist in subtropical forests, and both types of leaves are attacked by numerous insect herbivores. However, trees respond and defend themselves from herbivores in different ways, and these responses may vary between evergreen and deciduous species. We examined both the percentage of leaf area removed by herbivores as well as the percentage of leaves attacked by herbivores to evaluate leaf herbivore damage across 14 subtropical deciduous and evergreen tree species, and quantified plant defenses to varying intensities of herbivory. We found that there was no significant difference in mean percentage of leaf area removed between deciduous and evergreen species, yet a higher mean percentage of deciduous leaves were damaged compared to evergreen leaves (73.7% versus 60.2%). Although percent leaf area removed was mainly influenced by hemicellulose concentrations, there was some evidence that the ratio of non-structural carbohydrates:lignin and the concentration of tannins contribute to herbivory. We also highlight that leaf defenses to varying intensities of herbivory varied greatly among subtropical plant species and there was a stronger response for deciduous trees to leaf herbivore (e.g., increased nitrogen or lignin) attack than that of evergreen trees. This work elucidates how leaves respond to varying intensities of herbivory, and explores some of the underlying relationships between leaf traits and herbivore attack in subtropical forests.

Introduction: Septic shock in children is a highly heterogeneous syndrome involving different immune states and biological processes. We used a bioinformatics approach to explore the relationship between N6-methyladenosine (m6A) methylation and septic shock in children. Methods: A gene expression dataset including information on 98 children with septic shock was selected. To construct and evaluate a risk prediction model, machine learning was used to screen marker m6A regulators. Based on differentially expressed m6A regulators, molecular subtypes for paediatric septic shock were constructed. Subsequently, the differences in the m6Ascore, heterogeneity of immune cell infiltration, and heterogeneity of biological functions between the different subtypes were analyzed. Finally, real-time quantitative PCR (RT-qPCR) was performed to validate the expression of the marker m6A regulators. Results: Fifteen differentially expressed m6A regulators were identified. Six marker m6A regulators, including LRPPRC, ELAVL1, RBM15, CBLL1, FTO, and RBM15B, were screened using the random forest method. The risk prediction model for paediatric septic shock constructed using m6A markers had strong consistency and high clinical practicability. Two subtypes of paediatric septic shock have been identified based on the differential expression pattern of m6A regulators. Significant differences were observed in RNA epigenetics, immune statuses, and biological processes between the two m6A subtypes. Differentially expressed genes between the two subtypes were enriched in cell number homeostasis, redox responses, and innate immune system responses. Finally, the six marker m6A regulators were verified in additional samples. Conclusions: Based on the heterogeneity of m6A methylation-regulated genes, two different subtypes of septic shock in children with different RNA epigenetics, immune statuses, and biological processes were identified, revealing the heterogeneity of the disease largely attributable to differential m6A methylation. The findings will help explore and establish appropriate individualized treatments.

BackgroundQuestionnaires have been used in the past 2 decades to predict the diagnosis of vertigo and assist clinical decision-making. A questionnaire-based machine learning model is expected to improve the efficiency of diagnosis of vestibular disorders. ObjectiveThis study aims to develop and validate a questionnaire-based machine learning model that predicts the diagnosis of vertigo. MethodsIn this multicenter prospective study, patients presenting with vertigo entered a consecutive cohort at their first visit to the ENT and vertigo clinics of 7 tertiary referral centers from August 2019 to March 2021, with a follow-up period of 2 months. All participants completed a diagnostic questionnaire after eligibility screening. Patients who received only 1 final diagnosis by their treating specialists for their primary complaint were included in model development and validation. The data of patients enrolled before February 1, 2021 were used for modeling and cross-validation, while patients enrolled afterward entered external validation. ResultsA total of 1693 patients were enrolled, with a response rate of 96.2% (1693/1760). The median age was 51 (IQR 38-61) years, with 991 (58.5%) females; 1041 (61.5%) patients received the final diagnosis during the study period. Among them, 928 (54.8%) patients were included in model development and validation, and 113 (6.7%) patients who enrolled later were used as a test set for external validation. They were classified into 5 diagnostic categories. We compared 9 candidate machine learning methods, and the recalibrated model of light gradient boosting machine achieved the best performance, with an area under the curve of 0.937 (95% CI 0.917-0.962) in cross-validation and 0.954 (95% CI 0.944-0.967) in external validation. ConclusionsThe questionnaire-based light gradient boosting machine was able to predict common vestibular disorders and assist decision-making in ENT and vertigo clinics. Further studies with a larger sample size and the participation of neurologists will help assess the generalization and robustness of this machine learning method.

With the development of globalization and the more frequent cultural exchange worldwide, people have more opportunities to enjoy music from different cultures. Chinese traditional music is the inherent characteristic music of the Chinese people. Therefore, it's getting more and more important to translate Chinese traditional music terms properly so as to promote Chinese culture. However, the difficulties of English translation still exist, including the standardization of Chinese traditional music terms. From the perspective of Skopos Theory, this paper explores the translating methods of Chinese traditional music terms, which will be helpful for translators to achieve the different features of the Chinese traditional music terms in a structured way so as to improve cross-cultural communication ability and spread Chinese traditional culture. [ABSTRACT FROM AUTHOR]