Search

The Forkhead Box O (FOXO) gene plays a key role in various biological processes, such as growth, metabolism, development, immunity and longevity. Molting is an essential process for crustacean growth, which is mainly regulated by 20-hydroxyecdysone (20E) and molt-inhibiting hormone (MIH). Although the role of FOXO in regulating the immune response of crustaceans is well documented, its involvement in controlling crustacean molting remains unclear. In this study, a FOXO-like gene (designed as EsFOXO-like) was identified in Eriocheir sinensis, and the regulation of the 20E pathway by EsFOXO-like was also investigated. The coding sequence of EsFOXO-like was 852 bp, which consisted of 283 amino acids including a conserved Forkhead (FH) domain. EsFOXO-like shared high similarity with FOXO genes from other crustaceans, and the mRNA expression levels of the EsFOXO-like gene were highest in the hepatopancreas and lowest in the hemocytes. However, transcription and protein expression of the EsFOXO-like gene were found to be up-regulated only during the pre-molt stage in the hepatopancreas, with lower expression levels observed at the post-molt stage. To explore the role of EsFOXO-like in the 20E pathway, EsFOXO-like was firstly inhibited by a specific FOXO inhibitor (AS1842856) and then through an EsFOXO-like dsRNA injection, respectively, and the results showed that the relative expression levels of EsFOXO-like were notably decreased in the hepatopancreas after both the inhibitor and dsRNA treatments. The 20E concentration, the mRNA expression levels of the 20E receptors including the ecdysone receptor (EcR) and the retinoid-X receptor (RXR) and EsmTOR transcription in the AS1842856 group or the EsFOXO-RNAi group were all significantly higher than that in the control group, while the mRNA expression level of EsMIH was significantly decreased after EsFOXO-like inhibition. To further investigate whether the EsFOXO-like acts through mTOR or not, Rapamycin was administered to inhibit mTOR activity in EsFOXO-like inhibited crabs. The results revealed a significant reduction in the concentration of 20E and the expression level of EsMIH in the AS1842856 + Rapamycin group compared to the AS1842856 + DMSO group, accompanied by an increase in EsEcR and EsRXR expression. These findings collectively suggest that EsFOXO-like regulates the 20E pathway through mTOR, which offered valuable insights into the understanding of the molting process in crustaceans.

We herein present the design and synthesis of a structurally unique oxa-spirocyclic diphosphine ligand, termed as O-SDP. The diphosphine ligand O-SDP derived from oxa-spirocyclic diphenols (O-SPINO...

Asymmetric hydrogenation of α,β-unsaturated acids catalyzed by noble metals has been well established, whereas, the asymmetric hydrogenation with earth-abundant-metal was rarely reported. Here, we describe a cobalt-catalyzed asymmetric hydrogenation of α,β-unsaturated carboxylic acids. By using chiral cobalt catalyst bearing electron-donating diphosphine ligand, high activity (up to 1860 TON) and excellent enantioselectivity (up to >99% ee) are observed. Furthermore, the cobalt-catalyzed asymmetric hydrogenation is successfully applied to a broad spectrum of α,β-unsaturated carboxylic acids, such as various α-aryl and α-alkyl cinnamic acid derivatives, α-oxy-functionalized α,β-unsaturated acids, α-substituted acrylic acids and heterocyclic α,β-unsaturated acids (30 examples). The synthetic utility of the protocol is highlighted by the synthesis of key intermediates for chiral drugs (6 cases). Preliminary mechanistic studies reveal that the carboxy group may be involved in the control of the reactivity and enantioselectivity through an interaction with the metal centre., A large number of marketed drugs contains a chiral carboxylic acid scaffold. Here, the authors report the asymmetric hydrogenation of α,β-unsaturated carboxylic acids to α-chiral carboxylic acids using a cobalt catalyst bearing an electron-donating chiral diphosphine ligand.

The training of cable fault location methods lacks effective fault simulation combined with the cable itself. The equivalent insulation resistance of AC power cables with typical insulation faults was calculated and analyzed in this paper. The characteristics and feasibility of different defect simulation methods were compared. Based on engineering practice, a typical cable fault simulation device was designed. Studies have shown that the simulation of cable insulation faults by intrusive defects is not feasible in engineering. A cylindrical structure penetrating the cable insulation layer should be used to simulate the cable fault channel. Changing the resistivity of the faulty channel material can simulate the types of cable insulation faults with different equivalent resistances. The cable conductor or metal sheath is led out through the intervention mechanism and connected to the fault simulation components with different equivalent resistances, which can realize the equivalent of the cable fault outside the cable. The modular design of cable faults provides convenient conditions for cable fault location training.

We herein present a facile and column-free synthetic route toward a structurally unique oxa-spirocyclic diphenol, termed as O-SPINOL. Features of the synthesis include the construction of the all-carbon quaternary center at an early stage, a key double intramolecular SNAr step to introduce the spirocycles and the feasibility of operating on >100 g scale. Both enantiomers of O-SPINOL can be easily accessed through optical resolution with l-proline by control of the solvent. The chiral tridentate ligand O-SpiroPAP derived from O-SPINOL has been successfully synthesized and applied in the iridium-catalyzed asymmetric hydrogenation of bridged biaryl lactones under mild reaction conditions, providing valuable and enantioenriched axially chiral molecules in excellent yields and enantioselectivities (up to 99% yield and >99% ee). This method represents a rare example of constructing axially chiral molecules by direct reduction of esters with H2.

Bioaugmentation is an effective approach to remove the benzo[a]pyrene (BaP) from the environment, while its effect depends on the functional stability of the inoculated microorganisms. The aim of this study is to develop an approach on reducing the mutual exclusion of bacteria in the synthetic consortium in BaP degradation. Eight BaP-degrading bacterial strains were isolated from an enrichment with BaP as the sole carbon source. Two strains of Cupriavidus spp. exhibited greater degradation capacity (3.02-3.30 mg L-1 day-1) and selected as the "good degraders" in the synthetic consortia. Because of the mutual exclusion, the BaP-degradation capacity was reduced (1.47-1.77 mg L-1 day-1) when the other strains were added into "good degraders" through directly mixing the inocula. This mutual exclusion was mitigated through independent immobilization, in which the strains were embedded in sodium alginate before constructing the consortium. The consortium constructed by independent immobilization exhibited comparable BaP-degradation capacity with the high efficient strains. Therefore, the independent immobilization can be an advanced approach in functional consortium synthesis.

Elevated expression of forkhead/winged helix transcription factor FOXM1 are closely involved in cancer initiation, invasion and metastasis. It is a potentially suitable target for anticancer drug discovery and therapy. In this study, we investigated the expression and selection of human Foxm1c binding peptides and their inhibitions on MCF7 cancer cells. The protein of DNA binding domain of human FoxM1c(DBDFoxM1c) was expressed in prokaryotic system and then purified and later used as the target for binding peptide selection based on the phage random dodecapeptide library. The phages were enriched after four rounds of selection and 18 different peptide sequences were obtained. seven possible consensus peptide sequences WHL/Q/D/N, DL/HL/NY, SSLWN/E; HLD/YY/E; YH/LE/D/E/D; YPH/L/S and F/NY/FN/YL were identified and they were found to dock well to the 3D structure model of DBDFoxM1c by molecular docking. One representative peptide was designed and in vitro study revealed that the viability of MCF7 cancer cells could be reduced to 34.30 % at the concentration of 100 µg/ml of the peptide. In conclusion, the consensus peptide sequences identified in our study were newly reported and it is the first report of the screening of binding peptides targeting DBDFoxM1c. We expect that the results of these studies will result in future development of FoxM1c based lead peptide drug as well as the further understanding of DBDFoxM1c.

There is increasing evidence suggesting that S100P has a significant role in cancer, and is associated with poor clinical outcomes. The expression of S100P mRNA and protein in endometrial cancer and normal endometrium tissues was detected by real-time quantitative RT-PCR and immunohistochemistry. Moreover, we reduced the expression of S100P in HEC-1A and Ishikawa endometrial cancer cell lines by siRNA transfection. Based on the reduced S100P mRNA expression, we measured the effects of S100P on cellular proliferation by the cell-counting kit-8. Nuclear β-catenin protein level was detected by western blotting. Cyclin D1 and c-myc mRNA expression regulated by β-catenin was detected by real-time quantitative RT-PCR. We found that the expression of S100P mRNA and protein increased in endometrial cancer tissues compared with the normal endometrium. Local S100P expression progressively increased from pathologic differenciation grade 1 to 3. After reducing the S100P expression, the cellular proliferation ability, nuclear β-catenin protein level, cyclin D1 and c-myc mRNA levels reduced. It indicated that S100P could promote cell proliferation by increasing nuclear translocation of β-catenin. The expression of S100P mRNA and protein in endometrial cancer significantly increased and is associated with pathologic differenciation grade. S100P may promote endometrial cell proliferation by increasing nuclear translocation of β-catenin.