Discovery of 4-((3,4-dichlorophenyl)amino)-2-methylquinolin-6-ol derivatives as EGFR and HDAC dual inhibitors.

In patients with non-small cell lung cancer (NSCLC), the standard therapy consists of selective tyrosine kinase inhibitors that target epidermal growth factor receptors (EGFR). Nonetheless, their clinical utility is primarily limited by the development of resistance to drugs. HDAC inhibitors have been shown in studies to reduce the level of EGFR that is expressed and downregulate the EGFR-induced phosphorylation of AKT and ERK. Therefore, dual inhibitors of EGFR and HDAC provide a potential approach as combination treatment synergistically inhibited the growth of NSCLC. Herein, we examined the EGFR inhibition effect of twenty compounds which designed and synthesized by us previously. Among them, compounds 12c and 12d exhibited powerful antiproliferative activity against the NCI-H1975 cell line with IC50 values of 0.48 ± 0.07 and 0.35 ± 0.02 µM, correspondingly. In cell-free kinase assays, both 12c and 12d demonstrated target-specific EGFR inhibition against wild type (EGFRwt). Furthermore, the expression of EGFR and phosphorylation of the EGF-induced pathways were significantly suppressed under the treatment of 12c and 12d. Besides, both histones H3 and H4 exhibited increased levels of acetylation following 12c and 12d treatment. The animal experiments shown that 12d could prevent the growth of tumor, inhibited the expression of EGFR and the phosphorylation levels of p70 S6K, AKT and p38 MAPK in vivo, and did not cause organ damage to the mice during the experiment. Overall, the results illustrated that compound 12c and 12d could serve as effective EGFR and HDAC dual inhibitors in NSCLC cells. Our work offers an alternative strategy for NSCLC therapy.

Characterization of the complete mitochondrial genome of a forensically important beetle, Ptomascopus plagiatus (Coleoptera: staphylinidae: silphinae).

Ptomascopus plagiatus (Ménétriés, 1854) is a forensically important silphid species. In this study, we report on the mitochondrial genome of P. plagiatus. The complete mitochondrial genome of P. plagiatus is 17556 bp and contains 22 transfer RNA genes, 13 protein-coding genes (PCGs), two ribosomal RNA genes, and a 2953 bp noncoding region. The nucleotide composition of P. plagiatus is biased toward A and T (A + T: 77.46%). Phylogenetic analysis based on mitogenomic data supports that P. plagiatus is closely related to (Nicrophorus nepalensis Hope, 1831 + Nicrophorus vespilloides Herbst, 1783) within the subfamily Silphinae.

Species Composition and Succession of Necrophagous Insects on Small Buried Baits in China.

The postburial interval (PBI) can be inferred by using necrophagous insects colonizing the buried corpse. In different seasons, the species composition and succession of necrophagous insects on swine carrion (0.5-0.75 kg) buried at the depths of 30 cm and 60 cm in a Populus alba var. pyramidalis (Bunge, 1854) (Salicales: Salicaceae) grove of Shenyang, China from 2017 to 2019 were investigated. A total of 21 species of necrophagous insects belonging to 5 orders, 17 families were collected. Among them, the species of Phoridae and Platystomatidae were dominant at burial depth of 30 cm and 60 cm in summer and autumn. The species composition and time of colonization of necrophagous insects on the buried baits varied with seasons. Platystoma mandschuricum (Enderlein, 1937) (Diptera: Platystomatidae) and Aleochara puberula (Klug, 1833) (Coleoptera: Staphylinidae), the first arriving insects in spring, occurred on the baits for the longest time, from early June to early December. This work could provide reference data for the PBI estimation in Shenyang and similar geographical areas.

Characterization and Phylogenetic Analysis of the Complete Mitochondrial Genomes of Two Tiny Necrophagous Phorid Flies, Metopina sagittata and Puliciphora borinquenensis (Diptera: Phoridae).

The mitochondrial genome is frequently used for species identification and phylogenetic studies. In this study, we first sequenced and annotated the complete mitochondrial genomes of two phorid species that are forensically important in buried or enclosed environments: Metopina sagittata (Liu) and Puliciphora borinquenensis (Wheeler). The complete mitochondrial genome sequences of M. sagittata and P. borinquenensis were 15,640 bp with an A+T content of 75.97% and 15,429 bp with an A+T content of 75.38%, respectively. Their circular genomes both contained 13 protein-coding genes (PCGs), 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 control region located between rrnS and trnI which was 808 bp for M. sagittata and 746 bp for P. borinquenensis. All the PCGs of both species started with ATN codons except for cox1 which used TTG codon. In addition to the common stop codon TAA and TAG, the incomplete stop codon T was used in two PCGs (cox1 and nad4) of M. sagittata and five PCGs (cox1, cox2, cox3, nad5, and nad4) of P. borinquenensis. There were 3 and 10 mismatched base pairs in the tRNA secondary structures from M. sagittata and P. borinquenensis, respectively. Both maximum likelihood and Bayesian inference analyses indicated that Platypezidae and Phoridae are sister taxa. M. sagittata is closely related to P. borinquenensis within the subfamily Metopininae. This work enhances the databases of Phoridae genomes and contributes to the further study of species identification and phylogenetics of this family.

The complete mitochondrial genomes of Diplonevra funebris and Diplonevra peregrina (Diptera: Phoridae).

Diplonevra is one of the most important genera in the family Phoridae. This genus is mainly distributed in Palearctic region, and its species can be used to estimate the postmortem interval. In this study, we first present two mitochondrial genomes of common necrophagous species of this genus, Diplonevra funebris (Meigen, 1830) and Diplonevra peregrina (Wiedemann, 1830). Maximum-likelihood phylogenetic tree revealed that the genus Diplonevra is closely related to the genus Dohrniphora within the family Phoridae. This work expands the knowledge about the Phoridae genomes, and contributes to the further study of species identification and phylogenetics of this family.