Phosphoserine enhanced Cu-doped bioactive glass dynamic dual-network hydrogel for craniofacial bone defect repair

Flexible hydrogels containing various osteogenic inorganic constituents,which can accommodate complicated shape variations,are considered as ideal grafts for craniofacial bone defect reconstruction.However,in most hybrid hydrogels,poor interaction between the polymer network and particles has detrimental effects on hydrogel rheological and structural properties,clinical manipulation and repair efficacy.In this article,we designed and prepared a series of hyaluronic acid composite hydrogel containing Cu-doped bioactive glass(CuBG)and phosphoserine(PS),in which hyaluronic acid was modified by methacrylate groups and phenylboronic acid groups to form a double crosslinked network.PS acted as an interaction bridge of CuBG particles and HAMA-PBA network to improve the mechanical properties of the composite hydrogels.The CuBG/PS hydrogels exhibited suitable rheological properties(injectable,self-healing,shape-adaptable),bone tissue integrating ability and anti-bacterial property.Meanwhile,we found that CuBG and PS have synergistic effect on improving osteogenic efficiency both in vitro and in vivo,particularly when the ratio of CuBG to PS is lower than 3(9CB/3PS).This work provided a versatile and scalable approach to enhanced the interaction within inorganic particles and polymer network in hydrogels without extra modification on components.

The importance of a potential phosphorylation site in enamelin on enamel formation

Enamelin （ENAM） has three putative phosphoserines （pSers） phosphorylated by a Golgi-associated secretory pathway kinase （FAM20C） based on their distinctive Ser-x-Glu （S-x-E） motifs. Fam2OC-knockout mice show severe enamel defects similar to those in the Enam-knockout mice, implying an important role of the pSers in ENAM. To determine the role of pSer5s in ENAM, we characterized ENAMRgsc514 mice, in which Sers5 cannot be phosphorylated by FAM20C due to an E57〉Gs7 mutation in the S-x-E motif, The enamel microstructure of 4-week-old mice was examined by scanning electron microscopy. The teeth of 6-day-old mice were characterized by histology and immunohistochemistry. The protein lysates of the first lower molars of 4-day-old mice were analyzed by Western immunoblotting using antibodies against ENAM, ameloblastin and amelogenin. ENAMRgsc514 heterozygotes showed a disorganized enamel microstructure, while the homozygotes had no enamel on the dentin surface. The N-terminal fragments of ENAM in the heterozygotes were detained in the ameloblasts and localized in the mineralization front of enamel matrix, while those in the WT mice were secreted out of ameloblasts and distributed evenly in the outer 1/2 of enamel matrix. Surprisingly, the 15 kDa C-terminal fragments of ameloblastin were not detected in the molar lysates of the homozygotes. These results suggest that the phosphorylation of SerSS may be an essential posttranslational modification of ENAM and is required for the interaction with other enamel matrix molecules such as ameloblastin in mediating the structural organization of enamel matrix and protein-mineral interactions during enamel formation.

A mix & act liposomes of phospholipase A2-phosphatidylserine for acute brain detoxification by blood‒brain barrier selective-opening

In the treatment of central nervous system disease,the blood-brain barrier(BBB)is a major obstruction to drug delivery that must be overcome.In this study,we propose a brain-targeted delivery strat-egy based on selective opening of the BBB.This strategy allows some simple bare nanoparticles to enter the brain when mixed with special opening material;however,the BBB still maintains the ability to completely block molecules from passing through.Based on the screening of BBB opening and matrix delivery mate-rials,we determined that phospholipase A2-catalyzed 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine li-posomes can efficiently carry drugs into the brain immediately.At an effective dose,this delivery system is safe,especially with its effect on the BBB being reversible.This mix&act delivery system has a simple structure and rapid preparation,making it a strong potential candidate for drug delivery across the BBB.

Engineering and finetuning expression of SerC for balanced metabolic flux in vitamin B6 production

Vitamin B6 plays a crucial role in cellular metabolism and stress response,making it an essential component for growth in all known organisms.However,achieving efficient biosynthesis of vitamin B6 faces the challenge of maintaining a balanced distribution of metabolic flux between growth and production.In this study,our focus is on addressing this challenge through the engineering of phosphoserine aminotransferase(SerC)to resolve its redundancy and promiscuity.The enzyme SerC was semi-designed and screened based on sequences and predicted kcat values,respectively.Mutants and heterologous proteins showing potential were then fine-tuned to optimize the production of vitamin B6.The resulting strain enhances the production of vitamin B6,indicating that different fluxes are distributed to the biosynthesis pathway of serine and vitamin B6.This study presents a promising strategy to address the challenge posed by multifunctional enzymes,with significant implications for enhancing biochemical production through engineering processes.