The epidemic of Q fever in 2018 to 2019 in Zhuhai city of China determined by metagenomic next-generation sequencing

Q fever is a worldwide zoonosis caused by Coxiella burnetii (Cb). From January 2018 to November 2019, plasma samples from 2,382 patients with acute fever of unknown cause at a hospital in Zhuhai city of China were tested using metagenomic next-generation sequencing (mNGS). Of those tested, 138 patients (5.8%) were diagnosed with Q fever based on the presence of Cb genomic DNA detected by mNGS. Among these, 78 cases (56.5%) presented from Nov 2018 to Mar 2019, suggesting an outbreak of Q fever. 55 cases with detailed clinical information that occurred during the outbreak period were used for further analysis. The vast majority of plasma samples from those Cb-mNGS-positive patients were positive in a Cb-specific quantitative polymerase chain reaction (n = 38) and/or indirect immunofluorescence assay (n = 26). Mobile phone tracing data was used to define the area of infection during the outbreak. This suggested the probable infection source was Cb-infected goats and cattle at the only official authorized slaughterhouse in Zhuhai city. Phylogenic analysis based on genomic sequences indicated Cb strains identified in the patients, goat and cattle were formed a single branch, most closely related to the genomic group of Cb dominated by strains isolated from goats. Our study demonstrates Q fever was epidemic in 2018–2019 in Zhuhai city, and this is the first confirmed epidemic of Q fever in a contemporary city in China.     

Development of genome-wide SSR markers in melon with their cross-species transferability analysis and utilization in genetic diversity study

Simple sequence repeats (SSRs) are one of the most informative and widely used molecular markers in plant research. The melon draft genome has provided a powerful tool for SSR marker development in this species in which there are still not enough SSR markers. We therefore developed genome-wide SSR markers from melon, which were used for genetic diversity analysis in melon accessions and comparative mapping with cucumber and watermelon. A total of 44,265 microsatellites from the melon genome were characterized, of which 28,570 SSR markers were developed. In silico PCR analysis with these SSR markers identified 4002 and 1085 with one amplicon in cucumber and watermelon genome, respectively. With these cross-species transferable melon SSR markers, the chromosome synteny between melon and cucumber as well as watermelon was established, which revealed complicated mosaic patterns of syntenic blocks among them. We experimentally validated 384 SSR markers, from which 42 highly informative SSR ones were selected for genetic diversity and population structure analysis among 118 melon accessions. The large number of melon SSR markers developed in this study provides a valuable resource for genetic linkage map construction, molecular mapping, and marker-assisted selection (MAS) in melon. Furthermore, the cross-species transferable SSR markers could also be useful in various molecular marker-related studies in other closely related species in Cucurbitaceae family in which draft genomes are not yet available.     

Design, synthesis, and evaluation of 2-alkoxydihydrocinnamates as PPAR agonists

A series of 2-alkoxydihydrocinnamates were synthesized as PPARgamma and PPARalpha dual agonists. In vitro studies in cell model showed that these compounds were efficacious. Compound 1g was found to be a potent PPARalpha/gamma dual agonist and will be further evaluated for the treatment of type II diabetes.     

A carotenoid synthesis gene cluster from Algoriphagus sp. KK10202C with a novel fusion-type lycopene β-cyclase gene

A carotenoid synthesis gene cluster was isolated from a marine bacterium Algoriphagus sp. strain KK10202C that synthesized flexixanthin. Seven genes were transcribed in the same direction, among which five of them were involved in carotenoid synthesis. This cluster had a unique gene organization, with an isoprenoid gene, ispH (previously named lytB), being present among the carotenoid synthesis genes. The lycopene β-cyclase encoded by the crtY _cd gene appeared to be a fusion of bacterial heterodimeric lycopene cyclase CrtY_c and CrtY_d. This was the first time that a fusion-type of lycopene β-cyclase was reported in eubacteria. Heterologous expression of the Algoriphagus crtY _cd gene in lycopene-accumulating Escherichia coli produced bicyclic β-carotene. A biosynthesis pathway for monocyclic flexixanthin was proposed in Algoriphagus sp. strain KK10202C, though several of the carotenoid synthesis genes not linked with the cluster have not yet been cloned.     

Constitutive overexpression of the calcium sensor CBL5 confers osmotic or drought stress tolerance in Arabidopsis

Calcium serves as a critical messenger in many adaptation and developmental processes. Cellular calcium signals are detected and transmitted by sensor molecules such as calcium-binding proteins. In plants, the calcineurin B-like protein (CBL) family represents a unique group of calcium sensors and plays a key role in decoding calcium transients by specifically interacting with and regulating a family of CBL-interacting protein kinases (CIPKs). In this study, we report the role of Arabidopsis CBL5 gene in high salt or drought tolerance. CBL5 gene is expressed significantly in green tissues, but not in roots. CBL5 was not induced by abiotic stress conditions such as high salt, drought or low temperature. To determine whether the CBL5 gene plays a role in stress response pathways, we ectopically expressed the CBL5 protein in transgenic Arabidopsis plants (35S-CBL5) and examined plant responses to abiotic stresses. CBL5-overexpressing plants displayed enhanced tolerance to high salt or drought stress. CBL5 overexpression also rendered plants more resistant to high salt or hyperosmotic stress during early development (i.e., seed germination) but did not alter their response to abiscisic acid (ABA). Furthermore, overexpression of CBL5 alters the gene expression of stress gene markers, such as RD29A, RD29B and Kin1 etc. These results suggest that CBL5 may function as a positive regulator of salt or drought responses in plants.     

Effects of bufalin on the proliferation of human lung cancer cells and its molecular mechanisms of action

Bufalin, a naturally occurring small-molecule compound from Traditional Chinese Medicine (TCM) Chansu showed inhibitory effects against human prostate, hepatocellular, endometrial and ovarian cancer cells, and leukemia cells. However, whether or not bufalin has inhibitory activity against the proliferation of human non–small cell lung cancer (NSCLC) cells is unclear. The aim of this study is to study the effects of bufalin on the proliferation of NSCLC and its molecular mechanisms of action. The cancer cell proliferation was measured by MTT assay. The apoptosis and cell cycle distribution were analyzed by flow cytometry. The protein expressions and phosphorylation in the cancer cells were detected by Western blot analysis. In the present study, we have demonstrated that bufalin suppressed the proliferation of human NSCLC A549 cell line in time- and dose-dependent manners. Bufalin induced the apoptosis and cell cycle arrest by affecting the protein expressions of Bcl-2/Bax, cytochrome c, caspase-3, PARP, p53, p21WAF1, cyclinD1, and COX-2 in A549 cells. In addition, bufalin reduced the protein levels of receptor expressions and/or phosphorylation of VEGFR1, VEGFR2, EGFR and/or c-Met in A549 cells. Furthermore, bufalin inhibited the protein expressions and phosphorylation of Akt, NF-κB, p44/42 MAPK (ERK1/2) and p38 MAPK in A549 cells. Our results suggest that bufalin inhibits the human lung cancer cell proliferation via VEGFR1/VEGFR2/EGFR/c-Met–Akt/p44/42/p38-NF-κB signaling pathways; bufalin may have a wide therapeutic and/or adjuvant therapeutic application in the treatment of human NSCLC.     

Synthesis and anti-inflammatory activity of the major metabolites of imrecoxib

We have developed a novel and moderately selective COX-2 inhibitor, imrecoxib, as a new anti-inflammatory drug. We describe herein the preparation of the major metabolites M2 and M4 of imrecoxib, as well as the in vitro and in vivo activities of the two compounds. The results showed that both M2 and M4 are potential COXs inhibitors with a moderate COX-1/COX-2 selectivity, and their anti-inflammatory activity in vivo was equal to or slightly higher than the clinical celecoxib.