As a novel post-translational modification(PTM),lysine 2-hydroxyisobutyrylation(Khib)is considered to regulate gene transcriptional activities in eukaryotic cells;however,the functions of Khib-modified proteins in plants remain unknown.Here,we report that Khib is an evolutionarily-conserved PTM in wheat and its progenitors.A total of 3348 Khib sites on 1074 proteins are iden-tified in common wheat(Triticum aestivum L.)by using affinity purification and mass spectroscopy of 2-hydroxyisobutyrylome.Bioinformatic data indicate that Khib-modified proteins participate in a wide variety of biological and metabolic pathways.Immunoprecipitation confirms that Khib-modified proteins are present endogenously.A comparison of Khib and other main PTMs shows that Khib-modified proteins are simultaneously modified by multiple PTMs.Using mutagenesis experiments and co-immunoprecipitation assays,we demonstrate that Khib on K206 of phospho-glycerate kinase(PGK)is a key regulatory modification for its enzymatic activity,and mutation on K206 affects the interactions of PGK with its substrates.Furthermore,Khib modification of low-molecular-weight proteins is a response to the deacetylase inhibitors nicotinamide and tricho-statin.This study provides evidence to promote our current understanding of Khib in wheat plants,including the cooperation between Khib and its metabolic regulation.

To establish an injectable hydrogel containing Prussian blue (PB) nanospheres for photothermal therapy against cancer, PB nanospheres were prepared by one-pot synthesis and the thermosensitive Pluronic F127 was used as the hydrogel matrix. The PB nanospheres and the hydrogel were characterized by shape, particle size, serum stability, photothermal performance upon repeated 808 nm laser irradiation, as well as the rheological features. The effect of the PB nanospheres and the hydrogel were evaluated qualitatively and quantitatively in 4T1 mouse breast cancer cells. The retention, photothermal efficacy, therapeutic effects and systemic toxicity of the hydrogel were assessed in a tumor-bearing mouse model. The PB nanospheres had a diameter of about 150 nm and exhibited satisfactory serum stability, photo-heat convert ability and repeated laser exposure stability. The hydrogel encapsulation did not negatively influence the above features of the photothermal agent. The nanosphere-containing hydrogel showed a phase transition at body temperature and, as a result, a long retention time . The photothermal agent-embedded hydrogel displayed promising photothermal therapeutic effects in the tumor-bearing mouse model with little-to-no systemic toxicity after peritumoral administration.

MiR-142-3p has been reported to act as a tumor suppressor in breast cancer. However, the regulatory effect of miR-142-3p on drug resistance of breast cancer cells and its underlying mechanism remain unknown. Here, we found that miR-142-3p was significantly downregulated in the doxorubicin (DOX)-resistant MCF-7 cell line (MCF-7/DOX). MiR-142-3p overexpression increased DOX sensitivity and enhanced DOX-induced apoptosis in breast cancer cells. High-mobility group box 1 (HMGB1) is a direct functional target of miR-142-3p in breast cancer cells and miR-142-3p negatively regulated HMGB1 expression. Moreover, overexpression of HMGB1 dramatically reversed the promotion of apoptosis and inhibition of autophagy mediated by miR-142-3p up-regulation. In conclusion, miR-142-3p overexpression may inhibit autophagy and promote the drug sensitivity of breast cancer cells to DOX by targeting HMGB1. The miR-142-3p/HMGB1 axis might be a novel target to regulate the drug resistance of breast cancer patients.