PLUNC inhibits invasion and metastasis in nasopharyngeal carcinoma by inhibiting NLRP3 inflammasome activation.

Nasopharyngeal carcinoma (NPC) is a malignant tumor that occurs in the nasopharynx. Palate, lung, and nasal epithelium clone (PLUNC) has been identified as an early secreted protein that is specifically expressed in the nasopharynx. The aim of this study was to determine the role and mechanism of PLUNC in NPC. We used mRNA sequencing (seq) combined with ribosome-nascent chain complex (RNC)-seq to determine the biological role of PLUNC. The expression of epithelial-to-mesenchymal transition (EMT)-related molecules was detected by western blotting. Then, cell migration and invasion were detected by wound healing and Transwell chamber assays. NPC cells were injected into the tail vein of nude mice to explore the biological role of PLUNC in vivo. The sequencing results showed that PLUNC inhibited the progression of NPC and its expression was correlated with that of NOD-like receptors. Experiments confirmed that PLUNC inhibited the invasion and metastasis of NPC cells by promoting the ubiquitination degradation of NLRP3. PLUNC overexpression in combination with the treatment by MCC950, an inhibitor of NLRP3 inflammasome activation, was most effective in inhibiting NPC invasion and metastasis. In vivo experiments also confirmed that the combination of PLUNC overexpression and MCC950 treatment effectively inhibited the lung metastasis of NPC cells. In summary, our research suggested that PLUNC inhibited the invasion and metastasis of NPC by inhibiting NLRP3 inflammasome activation, and targeting the PLUNC-NLRP3 inflammasome axis could provide a new strategy for the diagnosis and treatment of NPC patients.

Naturally derived double-network hydrogels with application as flexible adhesive sensors.

Hydrogels have been widely used in the biomedical field, including wearable sensors and biological adhesives. However, achieving a balance between various functionalities, such as wet adhesion, stable conductivity, and biocompatibility, in one customized hydrogel has been a challenging issue. In this study, we developed a multifunctional hydrogel comprising recombinant human collagen (RHC) and aldehyde-modified sodium alginate (Ald-alginate), which was primarily crosslinked through a Schiff-base reaction and metal chelation. Due to the combination of a dynamic covalent crosslinking network (imine linkage between RHC and Ald-alginate) and a dynamic ionic crosslinking network (ionic bonding between Ca2+ and Ald-alginate), the hydrogel exhibited excellent self-healing and injectable behaviors. Benefiting from the high Ca2+ content, the hydrogel also attained antifreezing and conductivity properties. In addition to its excellent conductivity and biocompatibility, the hydrogel exhibited strong wet tissue adhesion ability and could adhere rapidly and strongly to the surfaces of various objects or biological tissues, forming a good sealing environment. Moreover, the hydrogel could be directly adhered to a tissue surface as a flexible sensor to accurately detect physiological signals. The versatility of this multifunctional hydrogel will open new avenues for biomedical applications, such as bioadhesives and biosensing.

APLNR inhibited nasopharyngeal carcinoma growth and immune escape by downregulating PD-L1.

BACKGROUND: APLNR is a G protein-coupled receptor and our previous study had revealed that APLNR could inhibit nasopharyngeal carcinoma (NPC) growth and metastasis. However, the role of APLNR in regulating PD-L1 expression and immune escape in NPC is unknown. METHODS: We analyzed the expression and correlation of APLNR and PD-L1 in NPC tissues and cells. We investigated the effect of APLNR on PD-L1 expression and the underlying mechanism in vitro and in vivo. We also evaluated the therapeutic potential of targeting APLNR in combination with PD-L1 antibody in a nude mouse xenograft model. RESULTS: We found that APLNR was negatively correlated with PD-L1 in NPC tissues and cells. APLNR could inhibit PD-L1 expression by binding to the FERM domain of JAK1 and blocking the interaction between JAK1 and IFNGR1, thus suppressing IFN-γ-mediated activation of the JAK1/STAT1 pathway. APLNR could also inhibit NPC immune escape by enhancing IFN-γ secretion and CD8+ T-cell infiltration and reducing CD8+ T-cell apoptosis and dysfunction. Moreover, the best effect was achieved in inhibiting NPC growth in nude mice when APLNR combined with PD-L1 antibody. CONCLUSIONS: Our study revealed a novel mechanism of APLNR regulating PD-L1 expression and immune escape in NPC and suggested that APLNR maybe a potential therapeutic target for NPC immunotherapy.

Understanding Emergent Complexity from a Single-Molecule Perspective.

Molecules, with structural, scaling, and interaction diversities, are crucial for the emergence of complex behaviors. Interactions are essential prerequisites for complex systems to exhibit emergent properties that surpass the sum of individual component characteristics. Tracing the origin of complex molecular behaviors from interactions is critical to understanding ensemble emergence, and requires insights at the single-molecule level. Electrical signals from single-molecule junctions enable the observation of individual molecular behaviors, as well as intramolecular and intermolecular interactions. This technique provides a foundation for bottom-up explorations of emergent complexity. This Perspective highlights investigations of various interactions via single-molecule junctions, including intramolecular orbital and weak intermolecular interactions and interactions in chemical reactions. It also provides potential directions for future single-molecule junctions in complex system research.

HECW1 restrains cervical cancer cell growth by promoting DVL1 ubiquitination and downregulating the activation of Wnt/ß-catenin signaling.

HECW1 belongs to ubiquitin ligase (E3) HECT family, and is found to be involved in tumorigenesis and tumor progression. However, the function of HECW1 in cervical cancer (CC) remains unknown. Clinical analysis showed that HECW1 is significantly decreased in CC tumor tissues. Ectopic expression of HECW1 suppressed cell growth, promoting cell cycle arrest and apoptosis in CC cells, while downregulation of HECW1 reversed these trends, impeded proliferation and accelerated cell cycle progression of CC cells. Overexpressing of HECW1 reduced mitochondrial membrane potential and the protein expression of voltage-dependent anion channel 1 (VDAC1). In addition, upregulation of HECW1 inhibited nuclear ß-catenin accumulation, downregulated ß-catenin/TCF/LEF-mediated transcriptional activity and the expression of downstream gene c-Myc, whereas inhibition of HECW1 received opposite results. Further results confirmed HECW1 affects the protein expression of dishevelled-1 (DVL1), a potent activator of Wnt/ß-catenin, and inhibition of HECW1 inhibited the ubiquitination of DVL1, upregulating its expression. Inhibition of DVL1 restrained the promotion effect of HECW1 suppression on cell proliferation. In vivo experiments also verified that HECW1 suppression promoted the tumor formation of CC cells. Summary, we demonstrated that HECW1 inhibits CC cell proliferation and tumor formation by downregulating DVL1 induced Wnt/ß-catenin signaling pathway activation.

Breaks for Precision Medicine in Cancer: Development and Prospects of Spatiotemporal Transcriptomics.

With the development of the social economy and the deepening understanding of cancer, cancer has become a significant cause of death, threatening human health. Although researchers have made rapid progress in cancer treatment strategies in recent years, the overall survival of cancer patients is still not optimistic. Therefore, it is essential to reveal the spatial pattern of gene expression, spatial heterogeneity of cell populations, microenvironment interactions, and other aspects of cancer. Spatiotemporal transcriptomics can help analyze the mechanism of cancer occurrence and development, greatly help precise cancer treatment, and improve clinical prognosis. Here, we review the integration strategies of single-cell RNA sequencing and spatial transcriptomics data, summarize the recent advances in spatiotemporal transcriptomics in cancer studies, and discuss the combined application of spatial multiomics, which provides new directions and strategies for the precise treatment and clinical prognosis of cancer.