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Background Halophila beccarii is one of the oldest two generations of seagrass plants and one of the 10 species of seagrass currently at risk of extinction worldwide. Therefore, how to effectively protect the H. beccarii resources from extinction is a huge challenge. Molecular biology research can provide a scientific basis for species conservation. So far, there has been no detailed analysis of the mitochondrial genome of the genus Halophila . Results The mitochondrial genome of H. beccarii was assembled into 28 circular chromosomes, ranging in length from 41,738 bp to 104,744 bp, with a total length of 1,964,072 bp and a GC content of 46.71%. It contains 39 genes, including 26 protein coding genes, 10 tRNA genes, and 3 rRNA genes. Repeat sequence analysis and prediction of RNA editing sites revealed a total of 850 dispersed repeats, 1,205 simple repeats, 61 tandem repeats, and 120 RNA editing sites. Analysis of codon usage indicates that codons ending in A/U are preferred. Gene migration between the mitochondrial genome and the chloroplast genome was observed through homologous fragment detection. In addition, Ka/Ks analysis showed that most protein coding genes in the mitochondrial genome experienced negative selection, while only the nad3 gene experienced potential positive selection in most Alismatales. Nucleotide polymorphism analysis revealed variations in each gene, with rpl10 being the most significant. In addition, comparative analysis shows that the GC content is conserved, but there are significant differences in the size and structure of mitochondrial genomes among different species of Alismatales. The phylogenetic analysis based on the mitochondrial genome reflects the exact evolutionary and taxonomic status of H. beccarii . Conclusion In this study, we sequenced and annotated the mitochondrial genome of H. beccarii , and compared it with the mitochondrial genomes of other plants in Alismatales. Our findings enrich the mitogenome database of seagrass plants and highlight the potential for mitochondrial genes to help decipher plant evolutionary history.

Ecologically, Halophila beccarii Asch. is considered as a colonizing or a pioneer seagrass species and a “tiny but mighty” seagrass species, since it may recover quickly from disturbance generally. The use of transcriptome technology can provide a better understanding of the physiological processes of seagrasses. To date, little is known about the genome and transcriptome information of H. beccarii . In this study, we used single molecule real-time (SMRT) sequencing to obtain full-length transcriptome data and characterize the transcriptome structure. A total of 11,773 of the 15,348 transcripts were successfully annotated in seven databases. In addition, 1573 long non-coding RNAs, 8402 simple sequence repeats and 2567 transcription factors were predicted in all the transcripts. A GO analysis showed that 5843 transcripts were divided into three categories, including biological process (BP), cellular component (CC) and molecular function (MF). In these three categories, metabolic process (1603 transcripts), protein-containing complex (515 transcripts) and binding (3233 transcripts) were the primary terms in BP, CC, and MF, respectively. The major types of transcription factors were involved in MYB-related and NF-YB families. To the best of our knowledge, this is the first report of the transcriptome of H. beccarii using SMRT sequencing technology.

As a key step of tumor lymphatic metastasis, lymphangiogenesis is regulated by VEGFC‐VEGFR3 signaling pathway mediated by immune cells, mainly macrophages, in the tumor microenvironment. However, little is known whether tumor associated neutrophils are involved in lymphangiogenesis. Here, it is found that TANs infiltration is increased in LN‐metastatic BCa and is associated with poor prognosis. Neutrophil depletion results in significant reduction in popliteal LN metastasis and lymphangiogenesis. Mechanistically, transcription factor ETV4 enhances BCa cells‐derived CXCL1/8 to recruit TANs, leading to the increase of VEGFA and MMP9 from TANs, and then facilitating lymphangiogenesis and LN metastasis of BCa. Moreover, phosphorylation of ETV4 at tyrosine 392 by tyrosine kinase PTK6 increases nuclear translocation of ETV4 and is essential for its function in BCa. Overall, the findings reveal a novel mechanism of how tumor cells regulate TANs‐induced lymphangiogenesis and LN metastasis and identify ETV4 as a therapeutic target of LN metastasis in BCa. Tumor‐associated neutrophil (TANs) infiltration is increased in lymph node (LN)‐metastatic bladder cancer and is associated with poor prognosis. Neutrophil depletion results in significant reduction in popliteal LN metastasis and lymphangiogenesis. Mechanistically, protein tyrosine kinase 6 (PTK6)‐mediated phosphorylation of ETS variant transcription factor (ETV4) enhances bladder cancer (BCa) cells‐derived chemokine C‐X‐C motif ligand (CXCL)1/8 to recruit TANs, leading to the increase of vascular endothelial growth factor A (VEGFA) and matrix metalloproteinase‐9 (MMP9), and then facilitating lymphangiogenesis and LN metastasis of bladder cancer.

The accurate and rapid estimation of the aboveground biomass (AGB) of rice is crucial to food security. Unmanned aerial vehicles (UAVs) mounted with hyperspectral sensors can obtain images of high spectral and spatial resolution in a quick and effective manner. Integrating UAV-based spatial and spectral information has substantial potential for improving crop AGB estimation. Hyperspectral remote-sensing data with more continuous reflectance information on ground objects provide more possibilities for band selection. The use of band selection for the spectral vegetation index (VI) has been discussed in many studies, but few studies have paid attention to the band selection of texture features in rice AGB estimation. In this study, UAV-based hyperspectral images of four rice varieties in five nitrogen treatments (N0, N1, N2, N3, and N4) were obtained. First, multiple spectral bands were used to identify the optimal bands of the spectral vegetation indices, as well as the texture features; next, the vegetation index model (VI model), the vegetation index combined with the corresponding-band textures model (VI+CBT model), and the vegetation index combined with the full-band textures model (VI+FBT model) were established to compare their respective rice AGB estimation abilities. The results showed that the optimal bands of the spectral and textural information for AGB monitoring were inconsistent. The red-edge and near-infrared bands demonstrated a strong correlation with the rice AGB in the spectral dimension, while the green and red bands exhibited a high correlation with the rice AGB in the spatial dimension. The ranking of the monitoring accuracies of the three models, from highest to lowest, was: the VI+FBT model, then the VI+CBT model, and then the VI model. Compared with the VI model, the R2 of the VI+FBT model and the VI+CBT model increased by 1.319% and 9.763%, respectively. The RMSE decreased by 2.070% and 16.718%, respectively, while the rRMSE decreased by 2.166% and 16.606%, respectively. The results indicated that the integration of vegetation indices and textures can significantly improve the accuracy of rice AGB estimation. The full-band textures contained richer information that was highly related to rice AGB. The VI model at the tillering stage presented the greatest sensitivity to the integration of textures, and the models in the N3 treatment (1.5 times the normal nitrogen level) gave the best AGB estimation compared with the other nitrogen treatments. This research proposes a reliable modeling framework for monitoring rice AGB and provides scientific support for rice-field management.

Seagrass meadows are among the four most productive marine natural ecosystems in the world. Zostera japonica (Z. japonica) is the most widely distributed species of seagrass in China. Nucleotide exchange factors (NEFs) promote the release of ADP during heat stress, accelerating the rate-limiting step of Heat shock protein 70 (Hsp70). Although NEFs play an important role in abiotic stress tolerance of plants, NEFs in seagrass have not been studied. In this study, we cloned Fes1 from Z. japonica (ZjFes1) by rapid amplification of the cDNA ends using RACE, and full length ZjFes1 was 1171 bp. It contained an 81 bp 5′-terminal untranslated region (UTR), 109 bp 3′-UTR and 981 bp open reading frame (ORF). The ORF (ZjFes1) was predicted to encode a polypeptide of 326 amino acids with theoretical molecular weight (MW) of 36.10 kDa and pI of 5.22. ZjFes1 shared 89% amino acid identity with Fes1 from Zostera marina (Z. marina). The transcriptional levels of ZjFes1 increased significantly 1 h after heat treatment. ZjFes1 was localized to the cytoplasm. Taken together, we found that ZjFes1 was a stress-inducible gene that may be involved in heat stress response. This study lays the foundation for further studies on the role of ZjFes1 in heat resistance.

Malignant tumors represent a significant worldwide health challenge, with elevated morbidity and mortality rates necessitating enhanced early identification and individualized treatment. Liposomes, as biomimetic lipid-based nanovesicles, have developed as a multifaceted platform for detecting and treating malignant tumors due to their excellent biocompatibility, stability, and membrane fusion properties. Circulating tumor markers, such as circulating tumor cells (CTCs), extracellular vesicles (EVs), circulating tumor proteins (CTPs), and circulating tumor nucleic acids (ctNAs), play a key role in early cancer diagnosis, disease progression monitoring, and personalized therapy. Liposome-based platforms enable effective molecular recognition, targeted detection, and signal amplification by targeting circulating tumor biomarkers, significantly increasing the potential for early tumor diagnosis and treatment. This review systematically summarizes advancements in the study of liposomes concerning circulating tumor markers, including applications in targeted recognition, early detection, and disease diagnosis, while discussing present problems and prospective applications of existing technology. Graphical Abstract Schematic illustration of this review’s content. (Created with BioRender.com ) 

Seagrass meadows are among the four most productive marine ecosystems in the world. Zostera japonica ( Z . japonica ) is the most widely distributed species of seagrass in China. However, there is no reference genome or transcriptome available for Z . japonica , impeding progress in functional genomic and molecular ecology studies in this species. Temperature is the main factor that controls the distribution and growth of seagrass around the world, yet how seagrass responds to heat stress remains poorly understood due to the lack of genomic and transcriptomic data. In this study, we applied a combination of second- and third-generation sequencing technologies to sequence full-length transcriptomes of Z . japonica . In total, we obtained 58,134 uniform transcripts, which included 46,070 high-quality full-length transcript sequences. We identified 15,411 simple sequence repeats, 258 long non-coding RNAs and 28,038 open reading frames. Exposure to heat elicited a complex transcriptional response in genes involved in posttranslational modification, protein turnover and chaperones. Overall, our study provides the first large-scale full-length trascriptome in Zostera japonica , allowing for structural, functional and comparative genomics studies in this important seagrass species. Although previous studies have focused specifically on heat shock proteins, we found that examination of other heat stress related genes is important for studying response to heat stress in seagrass. This study provides a genetic resource for the discovery of genes related to heat stress tolerance in this species. Our transcriptome can be further utilized in future studies to understand the molecular adaptation to heat stress in Zostera japonica .

Intratumor heterogeneity (ITH) is associated with anti-tumoral immune response and with the efficiency of cancer immunotherapy, yet overcoming ITH remains a significant challenge. Notably, cellular MYC (c-MYC) has been shown to be a pivotal orchestrator of this ITH progression. Here, we develop a c-MYC-based sensing circuit (cMSC) that is activated exclusively by aberrant c-MYC levels, along with an exosome-based cell-to-cell (CtC) system that augments communication among tumor cells, effectively targeting all cells in tumors circumventing the limitations imposed by ITH. Further expression of multifunctional immunostimulatory agents in these cMSC-reprogrammed cancer cells remodels the tumor microenvironment, enhancing selective T-cell-mediated oncolysis. Our cMSC/CtC platform specifically senses aberrant c-MYC expression and subsequently triggers a robust cancer immunotherapeutic response. These findings offer a promising avenue for targeting cancers via precisely sensing c-MYC, overcoming the limitations of ITH. Targeting tumors with c-MYC dysregulation is very challenging due to low MYC expression and intratumor heterogeneity. Here, the authors report a MYC-based gene circuitry that enhances immunotherapy response and tumor killing in bladder cancer.

Lymphatic metastasis is the most common pattern of bladder cancer (BCa) metastasis and has an extremely poor prognosis. Emerging evidence shows that ubiquitination plays crucial roles in various processes of tumors, including tumorigenesis and progression. However, the molecular mechanisms underlying the roles of ubiquitination in the lymphatic metastasis of BCa are largely unknown. In the present study, through bioinformatics analysis and validation in tissue samples, we found that the ubiquitin-conjugating E2 enzyme UBE2S was positively correlated with the lymphatic metastasis status, high tumor stage, histological grade, and poor prognosis of BCa patients. Functional assays showed that UBE2S promoted BCa cell migration and invasion in vitro, as well as lymphatic metastasis in vivo. Mechanistically, UBE2S interacted with tripartite motif containing 21 ( TRIM21 ) and jointly induced the ubiquitination of lipoma preferred partner ( LPP ) via K11-linked polyubiquitination but not K48- or K63-linked polyubiquitination. Moreover, LPP silencing rescued the anti-metastatic phenotypes and inhibited the epithelial-mesenchymal transition of BCa cells after UBE2S knockdown. Finally, targeting UBE2S with cephalomannine distinctly inhibited the progression of BCa in cell lines and human BCa-derived organoids in vitro, as well as in a lymphatic metastasis model in vivo, without significant toxicity. In conclusion, our study reveals that UBE2S , by interacting with TRIM21 , degrades LPP through K11-linked ubiquitination to promote the lymphatic metastasis of BCa, suggesting that UBE2S represents a potent and promising therapeutic target for metastatic BCa.

Background Lymphatic metastasis has been associated with poor prognosis in bladder cancer patients with limited therapeutic options. Emerging evidence shows that heat shock factor 1 (HSF1) drives diversified transcriptome to promote tumor growth and serves as a promising therapeutic target. However, the roles of HSF1 in lymphatic metastasis remain largely unknown. Herein, we aimed to illustrate the clinical roles and mechanisms of HSF1 in the lymphatic metastasis of bladder cancer and explore its therapeutic potential. Methods We screened the most relevant gene to lymphatic metastasis among overexpressed heat shock factors (HSFs) and heat shock proteins (HSPs), and analyzed its clinical relevance in three cohorts. Functional in vitro and in vivo assays were performed in HSF1‐silenced and ‐regained models. We also used Co‐immunoprecipitation to identify the binding proteins of HSF1 and chromatin immunoprecipitation and dual‐luciferase reporter assays to investigate the transcriptional program directed by HSF1. The pharmacological inhibitor of HSF1, KRIBB11, was evaluated in popliteal lymph node metastasis models and patient‐derived xenograft models of bladder cancer. Results HSF1 expression was positively associated with lymphatic metastasis status, tumor stage, advanced grade, and poor prognosis of bladder cancer. Importantly, HSF1 enhanced the epithelial‐mesenchymal transition (EMT) of cancer cells in primary tumor to initiate metastasis, proliferation of cancer cells in lymph nodes, and macrophages infiltration to facilitate multistep lymphatic metastasis. Mechanistically, HSF1 interacted with protein arginine methyltransferase 5 (PRMT5) and jointly induced the monomethylation of histone H3 at arginine 2 (H3R2me1) and symmetric dimethylation of histone H3 at arginine 2 (H3R2me2s). This recruited the WD repeat domain 5 (WDR5)/mixed‐lineage leukemia (MLL) complex to increase the trimethylation of histone H3 at lysine 4 (H3K4me3); resulting in upregulation of lymphoid enhancer‐binding factor 1 (LEF1), matrix metallopeptidase 9 (MMP9), C‐C motif chemokine ligand 20 (CCL20), and E2F transcription factor 2 (E2F2). Application of KRIBB11 significantly inhibited the lymphatic metastasis of bladder cancer with no significant toxicity. Conclusion Our findings reveal a novel transcriptional program directed by the HSF1‐PRMT5‐WDR5 axis during the multistep process of lymphatic metastasis in bladder cancer. Targeting HSF1 could be a multipotent and promising therapeutic strategy for bladder cancer patients with lymphatic metastasis.