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Persistent human papillomavirus (HPV) infection is associated with multiple malignancies. Developing therapeutic vaccines to eliminate HPV‐infected and malignant cells holds significant value. In this study, we introduced a lipid nanoparticle encapsulated mRNA vaccine expressing tHA‐mE7‐mE6. Mutations were introduced into E6 and E7 of HPV to eliminate their tumourigenicity. A truncated influenza haemagglutinin protein (tHA), which binds to the CD209 receptor on the surface of dendritic cells (DCs), was fused with mE7‐mE6 in order to allow efficient uptake of antigen by antigen presenting cells. The tHA‐mE7‐mE6 (mRNA) showed higher therapeutic efficacy than mE7‐mE6 (mRNA) in an E6 and E7+ tumour model. The treatment resulted in complete tumour regression and prevented tumour formation. Strong CD8+ T‐cell immune response was induced, contributing to preventing and curing of E6 and E7+ tumour. Antigen‐specific CD8+ T were found in spleens, peripheral blood and in tumours. In addition, the tumour infiltration of DC and NK cells were increased post therapy. In conclusion, this study described a therapeutic mRNA vaccine inducing strong anti‐tumour immunity in peripheral and in tumour microenvironment, holding promising potential to treat HPV‐induced cancer and to prevent cancer recurrence. [ABSTRACT FROM AUTHOR]

Summary: Self‐incompatibility plays a vital role in angiosperms, by preventing inbreeding depression and maintaining genetic diversity within populations. Following polyploidization, many angiosperm species transition from self‐incompatibility to self‐compatibility.Here, we investigated the S‐locus in Brassicaceae and identified distinct origins for the sRNA loci, SMI and SMI2 (SCR Methylation Inducer 1 and 2), within the S‐locus. The SMI loci were found to be widespread in Cruciferae, whereas the SMI2 loci were exclusive to Brassica species.Additionally, we discovered four major S‐haplotypes (BnS‐1, BnS‐6, BnS‐7, and BnS‐1300) in rapeseed. Overexpression of BnSMI‐1 in self‐incompatible Brassica napus ('S‐70S1300S6') resulted in a significant increase in DNA methylation in the promoter regions of BnSCR‐6 and BnSCR‐1300, leading to self‐compatibility. Conversely, by overexpressing a point mutation of BnSmi‐1 in the 'S‐70S1300S6' line, we observed lower levels of DNA methylation in BnSCR‐6 and BnSCR‐1300 promoters. Furthermore, the overexpression of BnSMI2‐1300 in the 'SI‐326S7S6' line inhibited the expression of BnSCR‐7 through transcriptional repression of the Smi2 sRNA from the BnS‐1300 haplotype.Our study demonstrates that the self‐compatibility of rapeseed is determined by S‐locus sRNA‐mediated silencing of SCR after polyploidization, which helps to further breed self‐incompatible or self‐compatible rapeseed lines, thereby facilitating the utilization of heterosis. [ABSTRACT FROM AUTHOR]

Cervical cancer, primarily squamous cell carcinoma, is the most prevalent gynecologic malignancy. Organoids can mimic tumor development in vitro, but current Matrigel inaccurately replicates the tissue-specific microenvironment. This limitation compromises the accurate representation of tumor heterogeneity. We collected para-cancerous cervical tissues from patients diagnosed with cervical squamous cell carcinoma (CSCC) and prepared uterine cervix extracellular matrix (UCEM) hydrogels. Proteomic analysis of UCEM identified several tissue-specific signaling pathways including human papillomavirus, phosphatidylinositol 3-kinase-AKT, and extracellular matrix receptor. Secreted proteins like FLNA, MYH9, HSPA8, and EEF1A1 were present, indicating UCEM successfully maintained cervical proteins. UCEM provided a tailored microenvironment for CSCC organoids, enabling formation and growth while preserving tumorigenic potential. RNA sequencing showed UCEM-organoids exhibited greater similarity to native CSCC and reflected tumor heterogeneity by exhibiting CSCC-associated signaling pathways including virus protein-cytokine, nuclear factor κB, tumor necrosis factor, and oncogenes EGR1, FPR1, and IFI6. Moreover, UCEM-organoids developed chemotherapy resistance. Our research provides insights into advanced organoid technology through native matrix hydrogels.