Emerging evidence has suggested that long noncoding RNAs (lncRNAs) play an essential role in the tumorigenesis of multiple types of cancer including gastric cancer (GC). However, the potential biological roles and regulatory mechanisms of lncRNA in response to cisplatin, which may be involved in cisplatin resistance, have not been fully elucidated. In this study, we identified a novel lncRNA, cisplatin resistance-associated lncRNA (CRAL), that was downregulated in cisplatin-resistant GC cells, impaired cisplatin-induced DNA damage and cell apoptosis and thus contributed to cisplatin resistance in GC cells. Furthermore, the results indicated that CRAL mainly resided in the cytoplasm and could sponge endogenous miR-505 to upregulate cylindromatosis (CYLD) expression, which further suppressed AKT activation and led to an increase in the sensitivity of gastric cancer cells to cisplatin in vitro and in preclinical models. Moreover, a specific small molecule inhibitor of AKT activation, MK2206, effectively reversed the cisplatin resistance in GC caused by CRAL deficiency. In conclusion, we provide the first evidence that a novel lncRNA, CRAL, could function as a competing endogenous RNA (ceRNA) to reverse GC cisplatin resistance via the miR-505/CYLD/AKT axis, which suggests that CRAL could be considered a potential predictive biomarker and therapeutic target for cisplatin resistance in gastric cancer.

Atractylodis rhizoma, is the dried rhizomes of Atractylodes lancea (Thunb.) DC. or A. chinensis (DC.) Koidz. Both of two are pharmacologically and economically important, while with differences in efficacy. Therefore, an authentication system is vital for evaluation the quality and discrimination adulteration of Atractylodis rhizoma. Fructooligosaccharides (FOS), which are regarded as functional ingredients in Atractylodis rhizoma, have not been used for quality control of Atractylodis rhizoma for shortage of reference compounds. A HPLC-ELSD method was developed for the quantification of FOS in Atractylodis rhizoma. And chemometrics analysis showed that 2 markers including content of degree of polymerization (DP) 12 and total content of DP 3-15 could be used as the main distinctive elements for quality evaluation of Atractylodis rhizome. Actually, the separation and purification of high DP FOS, such as DP 12, is still a challenge because of high polarity. Then DP 5-based qualification evaluation was investigated for quality control of Atractylodis rhizoma. The results showed that A. lancea and A. chinensis could be clearly separated. DP 5-based quantification method was credible and effectively adopted for solving the shortage of reference compounds and improving the quality control of Atractylodis rhizoma

Bacillus thuringiensis (BT) is distributed widely in the environment and utilized frequently for its highly specific toxins to target insect. However, BT is potentially pathogenic due to the high similarity between BT and Bacillus anthracis (BA). Meanwhile, there are reports that heavy metal pressure can promote the proliferation of antibiotic resistance in microorganisms through the co-selection of metal resistance genes (MRGs) and antibiotic resistance genes (ARGs). The aim of this work was revealed the MRGs and ARGs in a novel heavy metal tolerant and drug-resistant strain-B. thuringiensis HM-311, which was isolated from radiation and heavy metal-contaminated soil in Xinjiang (China). The genome of B. thuringiensis HM-311 was sequenced using a PacBio RS II platform and Illumina HiSeq 4000 platform at the Beijing Genomics Institute (BGI, Shenzhen, China). The total size of B. thuringiensis HM-311 genome was 6,019,481 bp with a GC content of 35.85%. 134 genes related to antibiotics resistance and 75 genes related to heavy metal resistance were predicted in the B. thuringiensis HM-311 genome, the main ARGs and MRGs were discussed. Moreover, 30 verified virulence factor genes and 297 predicted virulence factor genes were annotated in the B. thuringiensis HM-311 genome. This genome can be used as a reference sequence for comparative genomic studies, elucidating antibiotic resistance development and the relationship between antibiotic resistance genes and heavy metal resistance genes in B. thuringiensis.

The natural product pneumocandin B₀ is the precursor of the antifungal drug caspofungin. We found that replacing glucose in the initial fermentation medium with 20 g/L fructose is more conducive to pneumocandin B₀ production and biomass accumulation. In order to explore the mechanism of the different metabolic responses to fructose and glucose, we used each as the sole carbon source, and the results showed that fructose increased the total pneumocandin B₀ yield and biomass by 54.76 and 13.71%, respectively. Furthermore, we analyzed the differences of gene expression and metabolic pathways between the two different carbon sources by transcriptomic analysis. When fructose was used as the carbon source, genes related to the pentose phosphate pathway (PPP), glycolysis and branched-chain amino acid metabolism were significantly upregulated, resulting in increased intracellular pools of NADPH and acetyl-CoA in Glarea lozoyensis for cell growth and pneumocandin B₀ product synthesis. Interestingly, the pneumocandin B₀ biosynthetic gene cluster and the genes of the TCA cycle were significantly downregulated, while the FAS genes were significantly upregulated, indicating that more acetyl-CoA was used for fatty acid synthesis. In particular, we found that excessive synthesis of fatty acids caused lipid accumulation, and lipid droplets can sequester lipophilic secondary metabolites such as pneumocandin B₀ to reduce cell damage, which may also be an important reason for the observed increase of pneumocandin B₀ yield. These results provide new insights into the relationship between pneumocandin B₀ biosynthesis and carbon sources in G. lozoyensis. At the same time, this study provides important genomic information for improving pneumocandin B₀ production through metabolic engineering strategies in the future.