Rationale : Protein arginine methyltransferase 5 (PRMT5) is an oncogene that promotes tumor cell proliferation, invasion and metastasis. However, the underlying mechanisms by which PRMT5 contributes to the progression of cervical cancer and especially the tumor microenvironment remain poorly understood. Methods : PRMT5 expression level was analyzed by Q-PCR, western blot, immunohistochemistry, and TCGA database. The role of PRMT5 in tumor growth was observed by transplanted tumor models, and the function of T cells in tumor microenvironment and in vitro co-culture system was investigated through flow cytometry. The transcriptional regulation of PRMT5 was analyzed using luciferase reporter and chromatin immunoprecipitation (ChIP) assay. The therapeutic effect of PRMT5 inhibitor was evaluated in a cervical cancer cell line transplanted tumor model. Results : We observed that the mRNA and protein expression levels of PRMT5 were increased in cervical cancer tissues, and the high expression of PRMT5 was associated with poor outcomes in cervical cancer patients. The absence of PRMT5 significantly inhibited tumor growth in a cervical cancer transplanted tumor model, and importantly, PRMT5 absence in tumors led to increase the number and enhance the function of tumor infiltrating T cells. Mechanistically, PRMT5 enhanced the transcription of STAT1 through symmetric dimethylation of histone H3R2 and thus promoted PD-L1 expression in cervical cancer cells. Moreover, in an in vitro co-culture system, knockdown of PRMT5 in tumor cells could directly enhance the expression of IFN-γ, TNF-α and granzyme B in T cells. These results suggested that PRMT5 promoted the development of cervical cancer by the crosstalk between tumor cells and T cells. Furthermore, the PRMT5 inhibitor EPZ015666 treatment could suppress tumor growth in a cervical cancer transplanted tumor model. Conclusion : Our results clarify a new mechanism which PRMT5 knockdown in cervical cancer cells drives an antitumor function via reprogramming T cell-mediated response and regulating PD-L1 expression. Thus, our study highlights that PRMT5 may be a potential target for cervical cancer therapy.

The 1,3‐conjugated diynes are an important class of chemical intermediates, and the selective crosscoupling of terminal alkynes is an efficient chemical process for manufacturing asymmetrical 1,3‐conjugated diynes. However, it often occurs in homogenous conditions and costs a lot for reaction treatment. Herein, a copper catalyzed strategy is used to synthesize highly ordered mesoporous nitrogen‐doped carbon material (OMNC), and the copper species is in situ transformed into the copper single‐atom site with four nitrogen coordination (CuN4). These features make the CuN4/OMNC catalyst efficient for selective oxidative crosscoupling of terminal alkynes, and a wide range of asymmetrical and symmetrical 1,3‐diynes (26 examples) under mild conditions (40 °C) and low substrates ratio (1.3). Density functional theory (DFT) calculations reveal that the aryl–alkyl crosscoupling has the lowest energy barrier on the CuN4 site, which can explain the high selectivity. In addition, the catalyst can be separated and reused by simply centrifugation or filtration. This work can open a facile avenue for constructing single‐atom loaded mesoporous materials to bridge homogeneous and heterogeneous catalysis.

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N‐heterocycles are key structures for many pharmaceutical intermediates. The synthesis of such units normally is conducted under homogeneous catalytic conditions. Among all methods, aerobic oxidative aromatization is one of the most effective. However, in homogeneous conditions, catalysts are difficult to be recycled. Herein, we report a heterogeneous catalytic strategy with a mesoporous cobalt oxide as catalyst. The developed protocol shows a broad applicability for the synthesis of N‐heterocycles (32 examples, up to 99 % yield), and the catalyst presents high turnover numbers (7.41) in the absence of any additives. Such a heterogenous approach can be easily scaled up. Furthermore, the catalyst can be recycled by simply filtration and be reused for at least six times without obvious deactivation. Comparative studies reveal that the high surface area of mesoporous cobalt oxide plays an important role on the catalytic reactivity. The outstanding recycling capacity makes the catalyst industrially practical and sustainable for the synthesis of diverse N‐heterocycles.

Nanoporous carbons are very attractive for various applications including energy storage. Templating methods with assembled amphiphilic molecules or porous inorganic templates are typically used for the synthesis. Amongst the different members of this family, CMK‐5‐like structures that are constructed to consist of sub‐10 nm amorphous carbon nanotubes and ultrahigh specific surface area due to their thin pore walls, have the best properties in various respects. However, the fabrication of such hollow‐structured mesoporous carbons entails elaborately tailoring the surface properties of template pore walls and selecting specific carbon precursors. Thus, very limited cases are successful. Herein, we report a versatile and general silanol‐assisted surface‐casting method to create hollow‐structured mesoporous carbons and heteroatom‐doped derivatives with numerous organic molecules (e.g., furfuryl alcohol, resol, 2‐thiophene methanol, dopamine, tyrosine) and different structural templates. These carbon materials exhibit ultrahigh surface area (2400 m2 g–1), large pore volume (4.0 cm3 g–1), as well as satisfactory lithium‐storage capacity (1460 mAh g–1 at 0.1 A g–1), excellent rate capability (320 mAh g–1 at 5 A g–1), and very outstanding cycling performance (2000 cycles at 5 A g–1).This article is protected by copyright. All rights reserved