Sequential targeting of YAP1 and p21 enhances the elimination of senescent cells induced by the BET inhibitor JQ1.

Chondrosarcoma (CHS) is the second most common bone malignancy with limited therapeutic approaches. Our previous study has found that Yes associated protein 1 (YAP1) is downregulated in CHS cells treated with bromodomain and extraterminal domain (BET) inhibitor JQ1. However, the precise role of YAP1 in CHS is largely unknown. Herein, we found that YAP1 expression was upregulated in CHS tissues, and positively correlated with its grading score. Loss of YAP1 inhibited CHS proliferation and induced cellular senescence, while expression of YAP1 mutants revealed YAP1/TEA domain family member (TEAD)-dependent negative regulation of p21 and subsequent cellular senescence. These results were validated by in vivo experiments using stable shYAP1 cell lines. Mechanistically, negative regulation of p21 by YAP1 occurred post-transcriptionally via Dicer-regulated miRNA networks, specifically, the miR-17 family. Furthermore, we demonstrated that sequential targeting of YAP1 and p21 enhanced the elimination of JQ1-induced senescent cells in a Bcl-2-like 1 (Bcl-XL)/Caspase-3 dependent manner. Altogether, we unveil a novel role of YAP1 signaling in mediating CHS cell senescence and propose a one-two punch approach that sequentially targets the YAP1/p21 axis to eliminate senescent cells.

Half-sandwich cycloruthenated complexes from aryloxazolines: synthesis, structures, and catalytic activities.

Seven half-sandwich cycloruthenated complexes [Ru(p-cymene)LCl] (2a-2g) (L = 2-phenyl-2-oxazoline (2a), 2-p-tolyl-4,5-dihydrooxazole (2b), 4,4-dimethyl-2-phenyl-2-oxazoline (2c), 2-(4-chlorophenyl)-4,5-dihydrooxazole (2d), 2-(4-bromophenyl)-4,5-dihydrooxazole (2e), 2-(4-fluorophenyl)-4,5-dihydrooxazole (2f) and 2-(4-nitrophenyl)-4,5-dihydrooxazole (2g)) were synthesized and characterized. All half-sandwich cycloruthenated complexes were fully characterized by (1)H and (13)C NMR spectra, elemental analyses and infrared spectroscopy. The molecular structures of 2a, 2d and 2e were confirmed by single-crystal X-ray diffraction methods. These half-sandwich cycloruthenated complexes were employed in nitroarene reduction using sodium borohydride (NaBH4) as a reducing agent in ethanol at room temperature. The catalytic results indicate that half-sandwich cycloruthenated complexes show promising catalytic activity in nitroarene reduction with a broad substrate and varied functional group compatibility.

[Comprehensive evaluation of improving effects of different organic wastes on a newly reclaimed cultivated land].

There are many problems such as low soil organic matter, available nutrients and microbial activity, compaction, and poor tillage properties for a newly reclaimed cultivated land, and the establishment of a fast, effective measure for improving soil fertility quality is of importance to enhance the quality and production performance of the newly cultivated land. A field experiment was carried out to observe the effect of organic wastes on soil fertility of a newly reclaimed cultivated land, and compared the differences of different types of urban organic wastes. The field experiment included nine treatments, i.e., pig manure, chicken manure, rice straw, vegetable harvest residue, urban sludge, biogas residue, manure+rice straw compost, garbage compost and control without organic fertilizer at annual application rate of 30 t . hm-2, and ran for three consecutive years. The results showed that the application of each type of the eight organic wastes had obvious effects on improving soil fertility. Among them, pig manure, chicken manure, pig manure+rice straw compost, rice straw and biogas residue were the most effective to enhance the carbon pool management index of soil. The addition of pig manure+rice straw compost and biogas residue had the best effect on increasing the soil water stable aggregates and decreasing soil bulk density. Sewage sludge, pig manure+rice straw compost and garbage compost could enhance soil water holding capacity. Pig manure, chicken manure and pig manure+rice straw compost had most obvious effect on increasing soil available nutrients. All kinds of organic wastes increased the number of soil microorganisms and the activity of enzymes. There were some risk of soil heavy metals pollution.for the long-term application of sludge, garbage compost and manure. However, the impact of short-term application of the wastes on soil environmental quality was not obvious. Overall, effects of organic wastes on soil fertility decreased in the order of pig manure+rice straw compost>chicken manure>pig manure>biogas residue >garbage compost>rice straw>urban sludge>vegetable harvest residue, and the effects on soil pollution increased in the sequence of rice straw