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The phytohormone abscisic acid (ABA) is a major element involved in apple ( Malus domestica ) production because of its role in seed germination and early seedling development. The WRKY family, which is one of the largest families of transcription factors, plays an important role in ABA signaling in plants. However, the underlying molecular mechanisms of WRKY-mediated ABA sensitivity in apple are poorly understood. A genome-wide transcriptome analysis indicated that MdWRKY31 is a key factor induced by ABA. Quantitative real-time PCR showed that MdWRKY31 is induced by ABA in response to PEG4000, which is used to simulate drought. As a transcription factor, MdWRKY31 is localized in the nucleus. Ectopic expression of MdWRKY31 in Arabidopsis and Nicotiana benthamiana enhanced plant sensitivity to ABA. Overexpression of MdWRKY31 in apple roots and apple calli increased sensitivity to ABA, whereas repression of MdWRKY31 reduced sensitivity to ABA in the roots of ‘Royal Gala’. Electrophoretic mobility shift assays, chromatin immunoprecipitation PCR, and yeast one-hybrid assays indicated that MdWRKY31 directly binds to the promoter of MdRAV1 . Expression analyses of transgenic apple calli containing MdWRKY31 and pMdRAV1::GUS implied that MdWRKY31 represses the expression of MdRAV1 . We also found that MdRAV1 binds directly to the promoters of MdABI3 and MdABI4 and repressed their expression. Our findings reveal a new important regulatory mechanism of MdWRKY31-MdRAV1-MdABIs in the ABA signaling pathway in apple.

Stable Eu3+ doped single-layer rare-earth oxide nanosheets sol were successfully obtained via exfoliation of layer Y(1-X)EuxOBr in n-butanol solvent. After β-diketones modifying, novel inorganic/organic luminescent hybrids were successfully synthesized. At the mean time we discovered that the main charge transfer (Eu-O) excitation bands in nanosheets were replaced by more efficient π-π* electron transition excitation band s of the organic ligands in the hybrids. The emission bands of the 5D0-7F2 electric dipole transition in hybrids were enhanced greatly.

Gemcitabine plus cisplatin (GP) chemotherapy is the standard of care for nasopharyngeal carcinoma (NPC). However, the mechanisms underpinning its clinical activity are unclear. Here, using single-cell RNA sequencing and T cell and B cell receptor sequencing of matched, treatment-naive and post-GP chemotherapy NPC samples ( n  = 15 pairs), we show that GP chemotherapy activated an innate-like B cell (ILB)-dominant antitumor immune response. DNA fragments induced by chemotherapy activated the STING type-I-interferon-dependent pathway to increase major histocompatibility complex class I expression in cancer cells, and simultaneously induced ILB via Toll-like receptor 9 signaling. ILB further expanded follicular helper and helper type 1 T cells via the ICOSL–ICOS axis and subsequently enhanced cytotoxic T cells in tertiary lymphoid organ-like structures after chemotherapy that were deficient for germinal centers. ILB frequency was positively associated with overall and disease-free survival in a phase 3 trial of patients with NPC receiving GP chemotherapy ( NCT01872962 , n  = 139). It also served as a predictor for favorable outcomes in patients with NPC treated with GP and immunotherapy combined treatment ( n  = 380). Collectively, our study provides a high-resolution map of the tumor immune microenvironment after GP chemotherapy and uncovers a role for B cell-centered antitumor immunity. We also identify and validate ILB as a potential biomarker for GP-based treatment in NPC, which could improve patient management. Analysis of tumor samples from patients with nasopharyngeal carcinoma shows that gemcitabine plus cisplatin chemotherapy activates a unique population of innate-like B cells, which enhance the cytotoxic CD8 + T cell response and are associated with better clinical outcomes.

Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with extremely skewed ethnic and geographic distributions. Increasing evidence indicates that targeting the tumor microenvironment (TME) represents a promising therapeutic approach in NPC, highlighting an urgent need to deepen the understanding of the complex NPC TME. Here, we generated single-cell transcriptome profiles for 7581 malignant cells and 40,285 immune cells from fifteen primary NPC tumors and one normal sample. We revealed malignant signatures capturing intratumoral transcriptional heterogeneity and predicting aggressiveness of malignant cells. Diverse immune cell subtypes were identified, including novel subtypes such as CLEC9A + dendritic cells (DCs). We further revealed transcriptional regulators underlying immune cell diversity, and cell–cell interaction analyses highlighted promising immunotherapeutic targets in NPC. Moreover, we established the immune subtype-specific signatures, and demonstrated that the signatures of macrophages, plasmacytoid dendritic cells (pDCs), CLEC9A + DCs, natural killer (NK) cells, and plasma cells were significantly associated with improved survival outcomes in NPC. Taken together, our findings represent a unique resource providing in-depth insights into the cellular heterogeneity of NPC TME and highlight potential biomarkers for anticancer treatment and risk stratification, laying a new foundation for precision therapies in NPC.

Currently, there is no strong evidence of the well-established biomarkers for immune checkpoint inhibitors (ICIs) in nasopharyngeal carcinoma (NPC). Here, we aimed to reveal the heterogeneity of tumour microenvironment (TME) through virtual microdissection of gene expression profiles. An immune-enriched subtype was identified in 38% (43/113) of patients, which was characterized by significant enrichment of immune cells or immune responses. The remaining patients were therefore classified as a non-Immune Subtype (non-IS), which exhibited highly proliferative features. Then we identified a tumour immune evasion state within the immune-enriched subtype (18/43, 42%), in which high expression of exclusion- and dysfunction-related signatures was observed. These subgroups were designated the Evaded and Active Immune Subtype (E-IS and A-IS), respectively. We further demonstrated that A-IS predicted favourable survival and improved ICI response as compared to E-IS and non-IS. In summary, this study introduces the novel immune subtypes and demonstrates their feasibility in tailoring immunotherapeutic strategies.

AbstractThe present study aimed to detect the expression of interleukin-27 (IL-27) in tissues of oral lichen planus (OLP), oral leukoplakia (OLK), and oral squamous cell carcinoma (OSCC) and to investigate the possible role of IL-27 in the above diseases and whether it was involved in the onset and development of the tumor. Paraffin tissues from patients with OLP, OLK, and OSCC were collected, and the expression of IL-27 in the above tissues was detected by immunohistochemical (IHC) staining. Parameters were obtained from the images by the Image-Pro Plus (IPP) image analysis software, and statistical analysis was performed using relevant data. The expressions of IL-27 were significantly higher in specimens with OLP, OLK, and OSCC than those in the healthy group. In OLP, the expression of IL-27 was positively correlated with the degree of lymphocyte infiltration and basal cell liquefaction while independent of the clinical type. In OLK, the expression of IL-27 was positively correlated with abnormal epithelial cell proliferation. In OSCC, the expression of IL-27 was correlated with the degree of squamous cell differentiation and was independent of gender, TNM stage, and lymphatic metastasis. The expressions of IL-27 were significantly higher in tissues with severe OLP and OLK than that in the control group, while similar to that in highly differentiated OSCC. The expressions of IL-27 were significantly elevated in tissues with OLP, OLK, and OSCC, suggesting that IL-27 might be involved in the development of these diseases and play a role in the carcinogenesis of oral precancerous lesions.

Background Emerging evidence reveals that microbiota plays a crucial role in multiple cancers. Nasopharyngeal carcinoma (NPC) tissues harbour microbiota, highlighting the need to investigate the clinical implications of tissue-resident microbiota in the development of NPC. Here, we aim to clarify the specific profile of tissue-resident microbiota and its influence on NPC outcomes. Results This retrospective study included 491 NPC patients from Sun Yat-sen University Cancer Center (Guangzhou, China) and the Affiliated Hospital of Guilin Medical College (Guilin, China). We profiled the microbial composition of 343 NPC and 36 normal nasopharyngeal tissues through sequencing of the genes encoding the 16S rRNA subunit of bacterial ribosomes. There were significant differences in microbial composition, alpha diversity (Shannon index, P  = 0.007; Simpson index, P  = 0.036), and beta diversity (Bray–Curtis distance: R 2  = 0.016, F = 5.187, P  = 0.001; unweighted UniFrac distance: R 2  = 0.017, F = 5.373, P  = 0.001) between NPC and normal nasopharyngeal tissues. A bacterial signature comprising four risk bacterial genera, including Bacteroides , Alloprevotella , Parvimonas , and Dialister , was constructed in the training cohort ( n  = 171). Patients in the high-risk group had shorter disease-free (HR 2.80, 95% CI 1.51–5.18, P  < 0.001), distant metastasis-free (HR 4.00, 95% CI 1.77–9.01, P  < 0.001), and overall survival (HR 3.45, 95% CI 1.77–6.72, P  < 0.001) than those of patients in the low-risk group. Similar results were yielded in the internal validation ( n  = 172) and external validation ( n  = 148) cohorts. Integrated multi-omics analysis revealed that NPC tissues harbouring abundant risk bacteria were characterised by deficient immune infiltration, which was verified by multiplex immunohistochemistry. Conclusions This study developed and validated the applicability of a four-bacteria signature as a prognostic tool for NPC prognostication. Integrated multi-omics analysis further uncovered that the tumour immune microenvironment was perturbed by tissue-resident microbiota, which might pave the way towards the era of microbiota-targeted precision medicine for NPC. 9vn3tgs4Ha9buifpudN5P9 Video Abstract

Emerging evidence reveals that microbiota plays a crucial role in multiple cancers. Nasopharyngeal carcinoma (NPC) tissues harbour microbiota, highlighting the need to investigate the clinical implications of tissue-resident microbiota in the development of NPC. Here, we aim to clarify the specific profile of tissue-resident microbiota and its influence on NPC outcomes. This retrospective study included 491 NPC patients from Sun Yat-sen University Cancer Center (Guangzhou, China) and the Affiliated Hospital of Guilin Medical College (Guilin, China). We profiled the microbial composition of 343 NPC and 36 normal nasopharyngeal tissues through sequencing of the genes encoding the 16S rRNA subunit of bacterial ribosomes. There were significant differences in microbial composition, alpha diversity (Shannon index, P = 0.007; Simpson index, P = 0.036), and beta diversity (Bray-Curtis distance: R.sup.2 = 0.016, F = 5.187, P = 0.001; unweighted UniFrac distance: R.sup.2 = 0.017, F = 5.373, P = 0.001) between NPC and normal nasopharyngeal tissues. A bacterial signature comprising four risk bacterial genera, including Bacteroides, Alloprevotella, Parvimonas, and Dialister, was constructed in the training cohort (n = 171). Patients in the high-risk group had shorter disease-free (HR 2.80, 95% CI 1.51-5.18, P < 0.001), distant metastasis-free (HR 4.00, 95% CI 1.77-9.01, P < 0.001), and overall survival (HR 3.45, 95% CI 1.77-6.72, P < 0.001) than those of patients in the low-risk group. Similar results were yielded in the internal validation (n = 172) and external validation (n = 148) cohorts. Integrated multi-omics analysis revealed that NPC tissues harbouring abundant risk bacteria were characterised by deficient immune infiltration, which was verified by multiplex immunohistochemistry. This study developed and validated the applicability of a four-bacteria signature as a prognostic tool for NPC prognostication. Integrated multi-omics analysis further uncovered that the tumour immune microenvironment was perturbed by tissue-resident microbiota, which might pave the way towards the era of microbiota-targeted precision medicine for NPC.

Emerging evidence reveals that microbiota plays a crucial role in multiple cancers. Nasopharyngeal carcinoma (NPC) tissues harbour microbiota, highlighting the need to investigate the clinical implications of tissue-resident microbiota in the development of NPC. Here, we aim to clarify the specific profile of tissue-resident microbiota and its influence on NPC outcomes. This retrospective study included 491 NPC patients from Sun Yat-sen University Cancer Center (Guangzhou, China) and the Affiliated Hospital of Guilin Medical College (Guilin, China). We profiled the microbial composition of 343 NPC and 36 normal nasopharyngeal tissues through sequencing of the genes encoding the 16S rRNA subunit of bacterial ribosomes. There were significant differences in microbial composition, alpha diversity (Shannon index, P = 0.007; Simpson index, P = 0.036), and beta diversity (Bray-Curtis distance: R.sup.2 = 0.016, F = 5.187, P = 0.001; unweighted UniFrac distance: R.sup.2 = 0.017, F = 5.373, P = 0.001) between NPC and normal nasopharyngeal tissues. A bacterial signature comprising four risk bacterial genera, including Bacteroides, Alloprevotella, Parvimonas, and Dialister, was constructed in the training cohort (n = 171). Patients in the high-risk group had shorter disease-free (HR 2.80, 95% CI 1.51-5.18, P < 0.001), distant metastasis-free (HR 4.00, 95% CI 1.77-9.01, P < 0.001), and overall survival (HR 3.45, 95% CI 1.77-6.72, P < 0.001) than those of patients in the low-risk group. Similar results were yielded in the internal validation (n = 172) and external validation (n = 148) cohorts. Integrated multi-omics analysis revealed that NPC tissues harbouring abundant risk bacteria were characterised by deficient immune infiltration, which was verified by multiplex immunohistochemistry. This study developed and validated the applicability of a four-bacteria signature as a prognostic tool for NPC prognostication. Integrated multi-omics analysis further uncovered that the tumour immune microenvironment was perturbed by tissue-resident microbiota, which might pave the way towards the era of microbiota-targeted precision medicine for NPC.