Novel oxazolxanthone derivatives as a new type of α-glucosidase inhibitor: synthesis, activities, inhibitory modes and synergetic effect.

Xanthone derivatives have shown good α-glucosidase inhibitory activity and have drawn increased attention as potential anti-diabetic compounds. In this study, a series of novel oxazolxanthones were designed, synthesized, and investigated as α-glucosidase inhibitors. Inhibition assays indicated that compounds 4-21 bearing oxazole rings exhibited up to 30-fold greater inhibitory activity compared to their corresponding parent compound 1b. Among them, compounds 5-21 (IC50 = 6.3 ±â€¯0.4-38.5 ±â€¯4.6 µM) were more active than 1-deoxynojirimycin (IC50 = 60.2 ±â€¯6.2 µM), a well-known α-glucosidase inhibitor. In addition, the kinetics of enzyme inhibition measured by using Lineweaver-Burk analysis shows that compound 4 is a competitive inhibitor, while compounds 15, 16 and 20 are non-competitive inhibitors. Molecular docking studies showed that compound 4 bound to the active site pocket of the enzyme while compounds 15, 16, and 20 did not. More interestingly, docking simulations reveal that some of the oxazolxanthone derivatives bind to different sites in the enzyme. This prediction was further confirmed by the synergetic inhibition experiment, and the combination of representative compounds 16 and 20 at the optimal ratio of 4:6 led to an IC50 value of 1.9 ±â€¯0.7 µM, better than the IC50 value of 7.1 ±â€¯0.9 µM for compound 16 and 8.6 ±â€¯0.9 µM for compound 20.

Synthesis of N-heterocyclic carbene-PdCl2-(iso)quinoline complexes and their application in arylamination at low catalyst loadings.

A new type of N-heterocyclic carbene-PdCl2-(iso)quinoline complexes 3 were successfully achieved in acceptable to good yields from easily available starting materials under mild conditions, and their structures were unambiguously confirmed using X-ray single crystal diffraction. Furthermore, their catalytic activity toward Buchwald-Hartwig arylamination of aryl chlorides with primary and secondary amines was fully tested. Under the optimal reaction conditions, the expected arylated amines can be obtained in high to excellent yields at low catalyst loadings (0.005-0.05 mol%). It may be worth noting here that comparison of these complexes with other well-defined and easily available NHC-Pd(ii) complexes bearing different N-containing ancillary ligands was also carried out, showing their superior catalytic activity over all others.

[Epigenetic regulation of genomic imprinting in germline cells and preimplantation embryos].

Genomic imprinting is an epigenetic process that distinguishes parental alleles and results in specific expression of paternal and maternal genes. Imprints are acquired in the process of gametogenesis when genome-wide epigenetic reprogramming occurs and are maintained during early embryonic development. Therefore, the recognition and maintenance of imprints are very important in genome-wide reprogramming. In this review, we summarize the progresses of imprints removal in primordial germ cells (PGCs), imprints acquisition in parental PGCs, and imprints maintenance during early embryonic development. We also discuss the functional mechanisms of epigenetic factors which protect imprinted genes from whole genome DNA methylation.

Fine valence regulation of hydrated vanadium oxide as a novel cathode for stable potassium-ion storage.

Layered V10O24·nH2O with a large interlayer spacing of 14 Å is hydrothermally synthesized and used as a cathode for potassium-ion batteries. It exhibits a capacity of 110 mA h g-1 with a capacity retention of 99.2% over 700 cycles. Its storage mechanism is identified as pseudo-capacitive intercalation.

Epigenetic regulation of alternative splicing.

Alternative splicing (AS) serves as an additional regulatory process for gene expression after transcription, and it generates distinct mRNA species, and even noncoding RNAs (ncRNAs), from one primary transcript. Generally, AS can be coupled with transcription and subjected to epigenetic regulation, such as DNA methylation and histone modifications. In addition, ncRNAs, especially long noncoding RNAs (lncRNAs), can be generated from AS and function as splicing factors ("interactors" or "hijackers") in AS. Recently, RNA modifications, such as the RNA N6-methyladenosine (m6A) modification, have been found to regulate AS. In this review, we summarize recent achievements related to the epigenetic regulation of AS.

Relationship between glycated haemoglobin and subclinical atherosclerosis in obese children and adolescents.

OBJECTIVE: To explore the relationship between glycated haemoglobin A1C (HbA1C) and subclinical atherosclerosis as assessed by carotid intima-media thickness (cIMT) in Chinese Han obese children and adolescents without diabetes. METHODS: A total of 524 obese children and adolescents without diabetes were analysed. All participants underwent HbA1C measurements, oral glucose tolerance tests and ultrasound measurements of cIMT. The logistic regression models were implemented to evaluate the adjusted OR of HbA1C for increased cIMT. RESULTS: In obese boys, HbA1C was associated with increased cIMT independently of age, measurements of anthropometry, blood pressure, plasma lipid and lipoprotein, fasting plasma glucose, 2 h postchallenge glucose, uric acid and hepatic function. After adjustment for all these risk factors, the OR of increased cIMT for every 1% (11 mmol/mol) increase in HbA1C was 2.702 (95% CI 1.640 to 4.452). However, in girls, the major risk factor independently associated with cIMT was measurement of abdominal obesity instead of HbA1C. CONCLUSIONS: Our research suggests that the adoption of HbA1C as a diagnostic criterion of prediabetes and diabetes in obese boys may help to identify early macrovascular complications.