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Calcified aortic valve disease (CAVD) is a cardiovascular disease with increasing morbidity and mortality. The pathogenetic cellular mechanism is the phenotypic transition of aortic valve interstitial cells (VICs). Here, we explored the effect of berberine (BBR) on the phenotypic transition of VICs and elucidated the underlying molecular mechanisms, providing a theoretical basis in finding novel clinical treatments for CAVD.Calcific aortic valves and normal controls were collected for western blot and the results demonstrated that osteogenic and inflammatory markers were significantly up-regulated in calcific aortic valves. BBR inhibited inflammation and osteogenic differentiation of VICs under osteogenic conditions, as well as alkaline phosphatase activity and calcified nodule formation. Mechanistically, BBR could inhibit the activation of Smad1/5/8 and NF-κB pathways under OM conditions. LDN193189 and BAY11-7082, the inhibitor of Smad1/5/8 and NF-κB respectively, were added for further verification. Similarly, the osteogenic and fibrotic markers of VICs induced by osteogenic induction medium were decreased by LDN193189 and BAY11-7082. Western blot was used to examine upstream receptors of Smad1/5/8, the results showed that BBR inhibited the activation of Smad1/5/8 by downregulating ALK2 and ALK3.BBR decreased the inflammatory factors and suppressed the osteogenic differentiation of VICs, which might be associated with the inhibition of Smad1/5/8 and NF-κB signaling pathways.

A Ni-catalyzed addition of arylboronic acids to isatins was first developed. The reaction, driven by Ni(acac)2 and dppp as the phosphine ligand, gave 3-aryl-3-hydroxy-2-oxindoles in up to 97% yield. Scopes of benzyl-protected isatins and arylboronic acids were examined. Substituted phenylboronic acids along with fused-ring and heterocyclic boronic acids reacted with isatins smoothly. Preliminary asymmetric catalysis was investigated as well, showing moderate enantioselectivity. The mechanism was also described.

A novel, simple and sensitive photoelectrochemical (PEC) immunosensing platform was constructed for detecting N6-methyladenosine (m6A) based on the carboxylated CN and avidin functionalized Ru@SiO2 (ARS) nanocomposite. Herein, the N6-methyladenosine-5'-triphosphate (m6ATP) was selected as the detection target molecule, m6A antibody was used as recognition unit for m6A, the carboxylated g-C3N4 (CN) was not only used as the photoactive substance, but the substrate for the m6A antibody immobilization, ARS was synthesized and used as signal amplification unit to improve the photocurrent of CN, Phos-tag-biotin was employed as bridge of m6ATP and Ru@SiO2 through the specific interaction between phosphate group of m6ATP and Phos-tag, biotin and avidin, respectively. Under the optimal condition, the fabricated PEC biosensor showed a linear range of 0.01-10nM and high detection sensitivity with low detection limit of 3.23pM for m6ATP. Besides, the developed strategy was also successfully applied to evaluate the content of m6A in human serum samples.

By means of the direct condensation of

A novel, simple and sensitive photoelectrochemical (PEC) immunosensing platform was constructed for detecting N