OSMAC strategy integrated with molecular networking discovery peniciacetals A-I, nine new meroterpenoids from the mangrove-derived fungus Penicillium sp. HLLG-122.

Nine new highly oxygenated meroterpenoids, peniciacetals A-I (1-9), along with five known analogues (10-14) were isolated from the mangrove-derived fungus Penicillium sp. HLLG-122 based on the guidance of molecular networking and OSMAC approach. Peniciacetals A-B (1-2) were characterized with a unique 6/6/6/6/5 pentacyclic system possessing an unusual 4,6-dimethyl-2,5-dioxohexahydro-6-carboxy-4H-furo[2,3-b]pyran moiety. Peniciacetals C-D (3-4) possessed an uncommon 3,6-dimethyldihydro-4H-furo[2,3-b]pyran-2,5-dione unit with 6/6/6/5/6 fused pentacyclic skeleton. The structures and absolute configurations of new compounds were elucidated by HR-ESI-MS, 1D and 2D NMR spectroscopic data, X-ray diffraction analysis, and quantum chemical electronic circular dichroism (ECD) calculation. The plausible biosynthetic pathway of 1-9 were also proposed. Compound 14 showed good cytotoxicity against HepG2, MCF-7, HL-60, A549, HCT116 and H929 cell with IC50 values of 6.6, 14.8, 3.2, 5.7, 6.9 and 3.0 µM, respectively. Further research showed that the compound 14 induced necrosis or late apoptosis contributes to the HL-60 cells toxicity.

Identification of a Serum amyloid A gene and the association of SNPs with Vibrio-resistance and growth traits in the clam Meretrix meretrix.

Serum amyloid A (SAA), an acute response protein as well as an apolipoprotein, is considered to play crucial roles in both innate immunity and lipid metabolism. In this study, a SAA gene (MmSAA) was identified in the clam Meretrix meretrix. The full length DNA of MmSAA was 1407bp, consisting of three exons and two introns. The distribution of MmSAA in clam tissues was examined with the highest expression in hepatopancreas. In response to the Vibrio parahaemolyticus challenge, MmSAA mRNA showed significantly higher expression at 24 h post-challenge in experimental clams (P < 0.05). Forty-eight single nucleotide polymorphisms (SNPs) in the DNA partial sequence of MmSAA were discovered and examined for their association with Vibrio-resistance and growth traits, respectively. The single SNP association analysis indicated that five single SNPs (g.42, g.72, g.82, g.147 and g.165) were significantly associated with Vibrio-resistance (P < 0.05). Haplotype analysis produced additional support for association with the Chi-square values 6.393 (P = 0.012). Among the five selected SNPs, the effect of a missense mutation (g.82, A â†’ G) was detected by site-directed mutagenesis with fusion expression of protein assay, and the result showed that the recombinant plasmids containing wild-type pET30a-MmSAA had more inhibition effect than the mutant ones on the growth rate of the host bacteria. In addition, four growth traits of the clams in 09G3SPSB population were recorded and the SNP g.176 was found to be significantly associated with the growth traits with the Global score value 0.790 (P = 0.015). Our findings suggested that common genetic variation in MmSAA might contribute to the risk of susceptibility to Vibrio infection and might be associated with the growth traits in the clams M. meretrix, and more works are still needed to validate these SNPs as potential markers for actual selective breeding.

Analgesic efficacy of imrecoxib for postoperative pain following oral surgery: a prospective randomized, active-controlled, non-inferiority trial.

BACKGROUND: Imrecoxib, a novel cyclooxygenase (COX-2) selective non-steroidal anti-inflammatory drug (NSAID), has been approved in China for more than 9 years. This study aimed to assess the efficacy and safety of imrecoxib compared with celecoxib for patients with moderate or severe acute pain following oral surgery. METHODS: Patients with moderate or severe pain within 6 hours following surgery were enrolled in this randomized, active-control trial. Patients were randomly assigned (1:1) to receive either imrecoxib or celecoxib. Pain assessments on the visual analog scale, verbal rating scale, and pain relief were conducted at 0.5, 1, 2, 4, 6, 9, 12, and 24 hours after the first dose. Adverse events were also recorded. RESULTS: Eighty-seven patients were approached from November 2018 to August 2019. Of these, 60 were eligible for randomization. Ultimately, 56 patients (imrecoxib group, n=27; celecoxib group, n=29) were included in the analysis. The difference in total pain relief (TOTPAR) between the imrecoxib and celecoxib groups was 1.03 [95% confidence interval (CI): -1.31-3.77], with the lower bound of the CI above the specified non-inferiority boundary. No perioperative complications were observed in the imrecoxib group during the 24-hour period after the first dose. CONCLUSIONS: Imrecoxib could significantly relieve pain and has a non-inferior analgesic efficacy compared to celecoxib with good tolerance following oral surgery.

The polymorphisms of a MIF gene and their association with Vibrio resistance in the clam Meretrix meretrix.

Macrophage migration inhibitory factor (MIF) is an important proinflammatory cytokine that mediates both innate and adaptive immune responses. In this study, a homolog of MIF was identified in the clam Meretrix meretrix. Ten SNPs in the DNA partial sequence of MmMIF were found to be significantly associated with Vibrio resistance (P < 0.05). Distinct expression patterns of MmMIF among different haplotypes were observed after Vibrio challenge. The results showed that haplotypes did not affect MmMIF expression in the negative control group, while the expression of MmMIF in clams with Hap1 and Hap1/Hap2 was significantly lower than that with Hap2 at 24 h in the PBS-injected group but significantly higher than that with Hap2 in the Vibrio-injected group. The results also indicate that Hap1 and Hap1/Hap2 can specifically respond to mechanical stimulation while Hap2 can specifically respond to Vibrio infection. The effect of a missense mutation was detected by site-directed mutagenesis using fusion expression of the protein, which showed that the SNP g.737 (I > V) has no effect on redox activity and tautomerase activity. These studies identified a potential marker that is enriched in Vibrio-resistant clams that can be used for the genetic breeding of Meretrix meretrix.

Molecular cloning and characterization of cat, gpx1 and Cu/Zn-sod genes in pengze crucian carp (Carassius auratus var. Pengze) and antioxidant enzyme modulation induced by hexavalent chromium in juveniles.

Hexavalent chromium (Cr(6+)) is a common pollutant transient metal with high toxicity in the environment. The toxicological effects partly result from oxidative damage due to the production of excessive reactive oxygen species (ROS) in the reductive process of Cr(6+). To explore the influence of ROS induced directly by Cr(6+) on the oxidative stress generation and antioxidant system, the full length cDNAs of antioxidant-related genes cat, gpx1 and Cu/Zn-sod were successfully acquired from pengze crucian carp first and analyzed. Furthermore, the mRNA expression of the antioxidant genes encompassing catalase (cat), copper/zinc superoxide dismutase (Cu/Zn-sod) and glutathione peroxidase (gpx1), antioxidant enzyme activities of CAT, SOD, and GPx and total protein content were further studied in the gill, intestine and liver of pengze crucian carp (Carassius auratus var. Pengze) juveniles upon acute exposure to Cr(6+) at concentrations of 0.1, 1.0, 10 and 100 mg/L for 4 days. Differential significant changes of the antioxidant enzymes and gene expression were observed in different tissues. The findings contribute to better understanding the antioxidant mechanisms induced by Cr(6+) and selecting the organic-specific sensitive biomarkers to monitor the safety of the aquatic ecosystem.