The Aurora kinase family comprises three serine/threonine kinases, Aurora-A, -B and -C. Among these, Aurora-A and -B play central roles in mitosis, whereas Aurora-C executes unique roles in meiosis. Overexpression or gene amplification of Aurora kinases have been reported in a broad range of human malignancies, pointing to their role as potent oncogenes in tumorigenesis.Aurora kinases therefore represent promising targets for anticancer therapeutics. So far, a number of Aurora kinase inhibitors (AKIs) have been generated, of which some are currently undergoing clinical trials. Recent studies have unveiled novel unexpected functions of Aurora kinases during cancer development and the mechanisms underlying the anticancer actions of AKIs. In this review, we discuss the most recent advances in Aurora-A kinase research and targeted cancer therapy, focusing on the oncogenic roles and signaling pathways of Aurora-A kinases in contributing tumorigenesis, the recent preclinical and clinical AKI data and potential alternative routes for Aurora-A kinase inhibition.Key words: Aurora-A; Aurora kinase inhibitors (AKIs); targeted cancer therapy; mitosis; tumorigenesis 3 In mammals, the Aurora family of serine/threonine kinases consists of Aurora-A, -B and -C, which share a highly conserved catalytic domain containing auto-phosphorylating sites. The catalytic domain is flanked by a very short C-terminal tail and an N-terminal domain of variable lengths 1,2 . In the C-terminal regions of Auroras, there exists a short amino-acid peptide motif called "destruction box" (D-box). The D-box is recognized by the anaphase-promoting complex/cyclosome (APC/C) for degradation through the ubiquitin/proteasome-dependent pathway ( Fig. 1A). Despite their structural similarities, the expression patterns, cellular localization and physiological functions of these three Aurora kinases are largely distinct.Aurora-A and -B are commonly expressed in most cell types whereas Aurora-C is specially expressed in the testis. Both Aurora-A and -B play key roles in regulating cell-cycle progression from G2 through to cytokinesis. Aurora-C has a unique physiological role in spermatogenesis and functions as a chromosomal passenger protein similar to Aurora-B in mitosis 2 .Overexpression of Aurora-A and -B have been found in multiple types of cancer (Table 1), which function as oncogenes to promote tumorigenesis, providing potential targets for cancer therapy.However, comparatively little information is available regarding the roles of Aurora-C in cancer.In this review, we will focus on recent progress as well as the main unresolved issues associated with Aurora-A in cancer.4 1 FUNCTIONS OF AURORA-A In normal cells a. MitosisIn G1 phase, the level of Aurora-A is rarely detectable. During S phase, a small proportion of Aurora-A is first detected at centrosomes. At late G2 phase, Aurora-A accumulates evidently at centrosomes and becomes activated 3 . During prometaphase and metaphase, active Aurora-A localizes on bipolar spindles and spindle poles after...

Highly uniform hierarchical Mo-polydopamine hollow spheres are synthesized for the first time through a liquid-phase reaction under ambient temperature. A self-assembly mechanism of the hollow structure of Mo-polydopamine precursor is discussed in detail, and a determined theory is proposed in a water-in-oil system. Via different annealing process, these precursors can be converted into hierarchical hollow MoO /C and Mo C/C composites without any distortion in shape. Owing to the well-organized structure and nanosize particle embedding, the as-prepared hollow spheres exhibit appealing performance both as the anode material for lithium-ion batteries and as the catalyst for hydrogen evolution reaction (HER). Accordingly, MoO /C delivers a high reversible capacity of 940 mAh g at 0.1 A g and 775 mAh g at 1 A g with good rate capability and long cycle performance. Moreover, Mo C/C also exhibits an enhanced electrocatalytic performance with a low overpotential for HER in both acidic and alkaline conditions, as well as remarkable stability.

Due to its constitutive activity and ubiquitous distribution, CK2 is the most pleiotropic kinase among the individual members of the protein kinase superfamily. Identification of CK2 substrates is vital to decipher its role in biological processes. However, only a limited number of CK2 substrates were identified so far. In this study, we developed an integrated phosphoproteomics workflow to identify the CK2 substrates in large scale. First, in vitro kinase reactions with immobilized proteomes were combined with quantitative phosphoproteomics to identify in vitro CK2 phosphorylation sites, which leaded to identification of 988 sites from 581 protein substrates. To reduce false positives, we proposed an approach by comparing these in vitro sites with the public databases that collect in vivo phosphorylation sites. After the removal of the sites that were excluded in the databases, 605 high confident CK2 sites corresponding to 356 proteins were retained. The CK2 substrates identified in this study were based on the discovery mode, in which an unbiased overview of CK2 substrates was provided. Our result revealed that CK2 substrates were significantly enriched in the spliceosomal proteins, indicating CK2 might regulate the functions of spliceosome.

The study was conducted to compare the effects of different agro-wastes on the growth, yield, and nutritional composition of oyster mushrooms Pleurotus ostreatus (PO) and Pleurotus cystidiosus (PC). Seven substrate formulas including sawdust (SD), corncob (CC), sugarcane bagasse (SB) alone and in combination of 80 : 20, 50 : 50 ratio between SD and CC, SD and SB were investigated. The results indicated that different substrate formulas gave a significant difference in total colonization period, characteristics of fruiting bodies, yield, biological efficiency (BE), nutritional composition and mineral contents of two oyster mushrooms PO and PC. The results showed that increasing CC and SB reduced C/N ratio, and enhanced some mineral contents (Ca, P, and Mg) of substrate formulas. The increased amount of CC and SB of substrate formulas enhanced protein, ash, mineral contents (Ca, K, Mg, Mn, and Zn) of fruiting bodies of both mushrooms. Substrates with 100% CC and 100% SB were the most suitable substrate formulas for cultivation of oyster mushrooms PO and PC in which they gave the highest values of cap diameter, stipe thickness, mushroom weight, yield, BE, protein, fiber, ash, mineral content (Ca, K, and Mg) and short stipe length. However, substrate formula 100% CC gave the slowest time for the first harvest of both mushrooms PO and PC (46.02 days and 64.24 days, respectively). It is also found that the C/N ratio of substrate formulas has close correlation with total colonization period, mushroom weight, yield, BE and protein content of mushroom PO and PC.

Plants use both cell surface-resident pattern recognition receptors (PRRs) and intracellular nucleotide binding leucine-rich repeat (NLR) receptors to detect various pathogens. Plant PRRs typically recognize conserved pathogen-associated molecular patterns (PAMPs) to provide broad-spectrum resistance. By contrast, plant NLRs generally detect pathogen strain-specific effectors and confer race-specific resistance. Here, we demonstrate that the tomato () NLR Sw-5b confers broad-spectrum resistance against American-type tospoviruses by recognizing a conserved 21-amino acid peptide region within viral movement protein NSm (NSm). Sw-5b NB-ARC-LRR domains directly associate with NSm in vitro and in planta. Domain swap, site-directed mutagenesis and structure modeling analyses identified four polymorphic sites in the Sw-5b LRR domain that are critical for the recognition of NSm Furthermore, recognition of NSm by Sw-5b likely disturbs the residues adjacent to R927 in the LRR domain to weaken the intramolecular interaction between LRR and NB-ARC domains, thus translating recognition of NSm into activation of Sw-5b. Natural variation analysis of Sw-5b homologs from wild tomato species of South America revealed that the four polymorphic sites in the Sw-5b LRR domain were positively selected during evolution and are all necessary to confer resistance to tospovirus. The results described here provide a new example of a plant NLR mediating broad-spectrum resistance through recognition of a small conserved PAMP-like region within the pathogen effector.

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Application of transition metal phosphides (TMPs) for electrochemical energy conversion and storage has great potential to alleviate the energy crisis. Although there are many methods to get TMPs, it is still immensely challenging to fabricate hierarchical porous TMPs with superior electrochemical performances by a simple, green, and secure approach. Herein, we report a facile method to synthesize the CoP/C nanoboxes by pyrolysis of phytic acid (PA) cross-linked Co complexes that are acquired from reaction of PA and ZIF-67. The PA can not only slowly etch ZIF-67 and gain a hollow structure but also act as a source of phosphorus to prepare CoP/C nanoboxes. The CoP/C nanoboxes deliver an ultrahigh specific capacity (868 mA h g −1 at 100 mA g −1 ) and excellent cycle stability (523 mA h g −1 after 1000 cycles at 500 mA h g −1 ) when used as anode materials for lithium-ion batteries. Moreover, when used as an electrocatalyst for hydrogen evolution reaction, the CoP/C nanoboxes exhibit ultralow overpotential, small Tafel slope, and excellent durability in acidic media.

Objective: Leaflet thickening, fibrosis, and hardening are early pathological features of calcific aortic valve disease (CAVD). An inadequate understanding of the resident aortic valve cells involved in the pathological process may compromise the development of therapeutic strategies. We aim to construct a pattern of the human aortic valve cell atlas in healthy and CAVD clinical specimens, providing insight into the cellular origins of CAVD and the complex cytopathological differentiation process. Approach and Results: We used unbiased single-cell RNA sequencing for the high-throughput evaluation of cell heterogeneity in 34 632 cells isolated from 6 different human aortic valve leaflets. Cellular experiments, in situ localization, and bulk sequencing were performed to verify the differences between normal, healthy valves and those with CAVD. By comparing healthy and CAVD specimens, we identified 14 cell subtypes, including 3 heterogeneous subpopulations of resident valve interstitial cells, 3 types of immune-derived cells, 2 types of valve endothelial cells, and 6 novel valve-derived stromal cells found particularly in CAVD leaflets. Combining additional verification experiments with single-cell transcriptome profiling provided evidence of endothelial to mesenchymal transition involved in lesion thickening of the aortic valve leaflet. Conclusions: Our findings deconstructed the aortic valve cell atlas and suggested novel functional interactions among resident cell subpopulations. Our findings may provide insight into future targeted therapies to prevent CAVD.