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The TLRs of teleost fishes have distinct features and are highly diverse, but the duplication characteristics and expression patterns of the tlr22 gene remain unclear. Here, we identified paralogous tlr22 genes in 13 teleost fishes by screening available fish genomic resources and using molecular cloning. We then conducted comprehensive bioinformatics analyses and investigated spatiotemporal differences in the expression patterns of the tlr22 genes in G. eckloni. The results indicated that more than three paralogous tlr22 genes were possessed by some teleost fishes. Of these, tlr22c is specific to some subfamilies of the Cyprinidae (e.g., Barbinae, Cyprininae, Schizothoracinae, and Leuciscinae). Phylogenetic and syntenic analyses showed that the paralogous tlr22 genes originated from two single-gene duplication events. Molecular clock calculations dated the two gene duplication events at 49.5 and 39.3 MYA, which is before the common carp-specific genome duplication event and well after the fish-specific genome duplication. Gene duplication of tlr22 was followed by gene loss or pseudogene events in certain lineages. Spatiotemporal expression differences between the three duplicated tlr22 genes from G. eckloni suggested that these genes diverged functionally after gene duplication.

It is well known that liver cancer is a highly aggressive malignancy with poor prognosis. Andrographolide (AD), a major bioactive component of Andrographis paniculata (Burm. F.), is a potential anti-cancer pharmacophore and the synthesis of AD derivatives with better cytotoxicity to cancer cells has attracted considerable attentions. In the present study, we evaluated the in vivo inhibitory effects of ADN-9, a 15-benzylidene substituted derivative of AD, on the growth and metastasis of murine hepatoma H22 using an orthotopic xenograft model and a subcutaneous xenograft model, and we further studied the anti-angiogenic action and the related mechanisms of ADN-9 in vivo and in vitro. Importantly, ADN-9 remarkably suppressed the growth and metastasis of both orthotopic and subcutaneous xenograft tumors, and the serum AFP level in orthotopic hepatoma-bearing mice treated with 100mg/kg ADN-9 (ig.) was decreased to the normal level. We also found that ADN-9 showed stronger abilities than AD in shrinking tumors, suppressing the invasion and metastasis of H22 cells, decreasing the MVD and promoting tumor cell apoptosis in subcutaneous xenograft of mice. Additionally, ADN-9 exhibited stronger inhibitory activity than AD against the migration and VEGF-induced capillary-like tube formation in HUVECs, which was further proved to be associated with attenuating VEGF/VEGFR2/AKT signaling pathway. The present research provides the first evidence that a 15-substituted AD derivative is more promising than the parent compound in therapeutic treatment of liver cancer.

Based on a through bond energy transfer (TBET) between rhodamine and naphthalimide fluorophores, a fluorescent ratiometric chemosensor L was designed and prepared for highly selective detection of Fe 3+ in aqueous solution and in living EC109 cells. These significant changes in the fluorescence color could be used for naked-eye detection. The reversibility established the potential of the probe as chemosensor for Fe 3+ detection.

Based on fluorescent resonance energy transfer (FRET) between rhodamine and a naphthalimide fluorophore, a new ratiometric chemosensor L was synthesized and characterized. L exhibited high selectivity and excellent sensitivity in both absorbance and fluorescence detection of Hg2+ in aqueous solution with a broad pH span (1–10). The coordination of L with Hg2+ was chemically and partially reversible. The significant changes in the fluorescence color could be used for naked-eye detection. Furthermore, fluorescence imaging experiments of Hg2+ in living EC 109 cells demonstrated its value of practical applications in biological systems.

A novel rhodamine-based fluorescent probe L2 with two “S” groups was synthesized and characterized. As expected, L2 exhibited high selectivity and sensitivity for Hg2+ over other commonly coexistent metal ions. Its selectivity is excellent, and the detection limit was measured to be 1 ppm. The significant changes in the fluorescence color could be used for naked-eye detection. Furthermore, fluorescence imaging experiments of Hg2+ ions in living EC-109 cells demonstrated its value of practical applications in biological systems.

The excessive accumulation of hypochlorite could cause tissue damage and a range of diseases. However, the exact role of hypochlorite in biological activity remains elusive. In many of the reported probes for hypochlorite, DMSO which is an efficient HOCl and •OH scavenger was used as solvent. Besides, no fluorescent probes have been reported to quantify the accumulation of HOCl in living cells and in vivo. In order to reach this purpose, in this study, we report two mitochondria-targeted probes (L1 and L2) for detecting ClO−. These probes which were easy to be synthesized, shown high sensitivity and fast response (within 3 min) to ClO−. Fluorescent imaging of probes in MCF-7 cells and in zebrafish indicated that L1/L2 could be used for detecting ClO− in living cells and organisms. ClO− could also be used as a dual input logic gate for L1 and L2. Probe L2 could be used to monitor oxidative stress-related biological processes in nude mice.

A new rhodamine-based chemodosimeter( L2 ) was synthesized and characterized, which contained a tosyl group acted as a strong electron acceptor. As expected, L2 exhibited high selectivity and excellent sensitivity in both absorbance and fluorescence detection of Hg 2+ in aqueous solution. The coordination of L2 with Hg 2+ was chemically nonreversible and it was based on the fact that Hg 2+ exhibited a strong thiophilic affinity. Addition of Hg 2+ to an ethanol aqueous solution of L2 resulted in a color change from color-less to obvious pink color, these significant changes in color could be used for naked-eye detection. Furthermore, fluorescence imaging experiments of Hg 2+ ions in living MGC803 cells demonstrated its value of practical applications in biological systems.