Antibacterial adhesives have favorable prospects to inhibit biofilms and secondary caries. The objectives of this study were to investigate the antibacterial effect of dental adhesives containing dimethylaminododecyl methacrylate (DMADDM) on different bacteria in controlled multispecies biofilms and its regulating effect on development of biofilm for the first time. Antibacterial material was synthesized, and Streptococcus mutans, Streptococcus gordonii, and Streptococcus sanguinis were chosen to form multispecies biofilms. Lactic acid assay and pH measurement were conducted to study the acid production of controlled multispecies biofilms. Anthrone method and exopolysaccharide (EPS):bacteria volume ratio measured by confocal laser scanning microscopy were performed to determine the EPS production of biofilms. The colony-forming unit counts, scanning electron microscope imaging, and dead:live volume ratio decided by confocal laser scanning microscopy were used to study the biomass change of controlled multispecies biofilms. The TaqMan real-time polymerase chain reaction and fluorescent in situ hybridization imaging were used to study the proportion change in multispecies biofilms of different groups. The results showed that DMADDM-containing adhesive groups slowed the pH drop and decreased the lactic acid production noticeably, especially lactic acid production in the 5% DMADDM group, which decreased 10- to 30-fold compared with control group (P < 0.05). EPS was reduced significantly in 5% DMADDM group (P < 0.05). The DMADDM groups reduced the colony-forming unit counts significantly (P < 0.05) and had higher dead:live volume ratio in biofilms compared with control group (P < 0.05). The proportion of S. mutans decreased steadily in DMADDM-containing groups and continually increased in control group, and the biofilm had a more healthy development tendency after the regulation of DMADDM. In conclusion, the adhesives containing DMADDM had remarkable antimicrobial properties to serve as "bioactive" adhesive materials and revealed its potential value for antibiofilm and anticaries clinical applications.

Dental caries is closely associated with the microbial disequilibrium between acidogenic/aciduric pathogens and alkali-generating commensal residents within the dental plaque. Fluoride is a widely used anticaries agent, which promotes tooth hard-tissue remineralization and suppresses bacterial activities. Recent clinical trials have shown that oral hygiene products containing both fluoride and arginine possess a greater anticaries effect compared with those containing fluoride alone, indicating synergy between fluoride and arginine in caries management. Here, we hypothesize that arginine may augment the ecological benefit of fluoride by enriching alkali-generating bacteria in the plaque biofilm and thus synergizes with fluoride in controlling dental caries. Specifically, we assessed the combinatory effects of NaF/arginine on planktonic and biofilm cultures of Streptococcus mutans, Streptococcus sanguinis, and Porphyromonas gingivalis with checkerboard microdilution assays. The optimal NaF/arginine combinations were selected, and their combinatory effects on microbial composition were further examined in single-, dual-, and 3-species biofilm using bacterial species-specific fluorescence in situ hybridization and quantitative polymerase chain reaction. We found that arginine synergized with fluoride in suppressing acidogenic S. mutans in both planktonic and biofilm cultures. In addition, the NaF/arginine combination synergistically reduced S. mutans but enriched S. sanguinis within the multispecies biofilms. More importantly, the optimal combination of NaF/arginine maintained a "streptococcal pressure" against the potential growth of oral anaerobe P. gingivalis within the alkalized biofilm. Taken together, we conclude that the combinatory application of fluoride and arginine has a potential synergistic effect in maintaining a healthy oral microbial equilibrium and thus represents a promising ecological approach to caries management.

VAI could independently predict DM in the Chinese study population, although the predictive power was not higher than that of simple anthropometric measures (BMI and WC). Our study does not support the clinical application of VAI; however, more studies based on different ethnic groups still need to be performed.

Whether for cancer diagnosis or single-cell analysis, it remains a major challenge to isolate the target sample cells from a large background cell for high-efficiency downstream detection and analysis in an integrated chip. Therefore, in this paper, we propose a 3D-stacked multistage inertial microfluidic sorting chip for high-throughput enrichment of circulating tumor cells (CTCs) and convenient downstream analysis. In this chip, the first stage is a spiral channel with a trapezoidal cross-section, which has better separation performance than a spiral channel with a rectangular cross-section. The second and third stages adopt symmetrical square serpentine channels with different rectangular cross-section widths for further separation and enrichment of sample cells reducing the outlet flow rate for easier downstream detection and analysis. The multistage channel can separate 5  μ m and 15  μ m particles with a separation efficiency of 92.37% and purity of 98.10% at a high inlet flow rate of 1.3 mL/min. Meanwhile, it can separate tumor cells (SW480, A549, and Caki-1) from massive red blood cells (RBCs) with a separation efficiency of >80%, separation purity of >90%, and a concentration fold of ~20. The proposed work is aimed at providing a high-throughput sample processing system that can be easily integrated with flowing sample detection methods for rapid CTC analysis.

Valproic acid is an anticonvulsant, which is also widely used for treating psychiatric disorders. Some clinical trials have demonstrated benefits of valproic acid augmentation therapy in schizophrenia. Interindividual variability in valproic acid dose and serum concentration may reflect functional consequences of genetic polymorphisms in genes encoding drug-metabolizing enzymes. The aim of this study was to determine the relationship between serum concentrations of valproic acid and single nucleotide polymorphisms of the cytochrome P450 (CYP) 2C19 gene in patients with schizophrenia. All patients had been receiving fixed dose of valproic acid for at least 2 weeks. The daily doses were 0.5–1.5 g. No other drugs except olanzapine were coadministered. Serum concentrations of valproic acid were measured using the ultra-high performance liquid chromatography method with mass-spectrometric detection. The CYP2C19 (CYP2C19*2 G681A rs4244285 and CYP2C19*3 G636A rs4986893) genotypes were identified by real-time PCR analyses. The mean concentration/dose ratios of valproic acid were significantly higher in patients with CYP2C19 *1/*2 genotype (P < 0.01) or CYP2C19 *2/*3 genotype (P < 0.01) than in those with CYP2C12 *1/*1 genotype. The mean concentration/dose ratios of valproic acid were significantly higher in patients with 1 (P < 0.01) or 2 (P < 0.01) mutated alleles for CYP2C19 than in those without mutated alleles. And the post hoc analysis revealed that the result has acceptable statistical (power (1 – β) = 0.8486 at type I  level of 0.05) to support the observed significant associations for CYP2C19 SNPs and serum C/D ratios of valproic acid. The findings of this study suggest that the genetic polymorphisms of CYP2C19 significantly affect the steady-state serum concentrations of valproic acid in Chinese Han population. The determination of the CYP2C19 genotypes may be useful for dosing adjustment in schizophrenia patients on valproic acid therapy.

Pachydermoperiostosis (PDP), also named primary hypertrophic osteoarthropathy (PHO: MIM 167100), is a rare genetic disease characterized by 3 major symptoms: pachydermia including cutis verticis gyrata (CVG), periostosis, and digital clubbing. Additional clinical signs and symptoms include seborrheic hyperplasia, hyperhidrosis, and arthropathy. This article is protected by copyright. All rights reserved.

Shp2 negatively regulates thrombus stability under pathological shear rate. Shp2 suppresses TXA2 receptor‐mediated platelet dense granule secretion. Through αIIbβ3 outside‐in signaling, Shp2 targets calmodulin‐dependent activation of Akt. Shp2 may serve to prevent the formation of unwanted occlusive thrombi. Summary BackgroundPerpetuation is the final phase of thrombus formation; however, its mechanisms and regulation are poorly understood. ObjectiveTo investigate the mechanism of Shp2 in platelet function and thrombosis. Methods and resultsWe demonstrate that the platelet‐expressed Src homology region 2 domain‐containing protein tyrosine phosphatase Shp2 is a negative regulator of thrombus stability under high shear stress. In a ferric chloride‐induced mesenteric arteriole thrombosis model, megakaryocyte/platelet‐specific Shp2‐deficient mice showed less thrombi shedding than wild‐type mice, although their occlusion times were comparable. In accordance with this in vivo phenotype, a microfluidic whole‐blood perfusion assay revealed that the thrombi formed on collagen surfaces by Shp2‐deficient platelets were more stable under high shear rates than those produced by wild‐type platelets. Whereas Shp2 deficiency did not alter platelet responsiveness towards thrombin, ADP and collagen stimulation, Shp2‐deficient platelets showed increased dense granule secretion when stimulated by the thromboxane A2 analog U46619. Shp2 appears to act downstream of integrin αIIbβ3 outside‐in signaling, inhibiting the phosphorylation of Akt (Ser473 and Thr308) and dense granule secretion. Calmodulin was also shown to bind both Shp2 and Akt, linking Shp2 to Akt activation. ConclusionsPlatelet Shp2 negatively regulates thrombus perpetuation under high shear stress. This signaling pathway may constitute an important mechanism for the prevention of unwanted occlusive thrombus formation, without dramatically interfering with hemostasis.

Aims:  Food‐grade microemulsions have been of increasing interest to researchers as potential delivery systems for bioactive compounds. However, food‐grade microemulsions are difficult to formulate and no microemulsion has been documented for antifungal purpose. The physicochemical characterization of a food‐grade glycerol monolaurate (GML)/ethanol (EtOH)/Tween 80/potassium sorbate (PS)/water microemulsion system and the antifungal activities against Aspergillus niger and Penicillium italicum have been studied in this paper. Methods and Results:  The influence of EtOH and PS on oil solubilization capability was clearly reflected in the phase behaviour of U‐type microemulsion systems. One dilution‐stable formulation ME (GML/EtOH/Tween 80/PS/water = 3 : 3 : 3·5 : 10·5 : 16) was selected. After 4 days of incubation, ME showed 80%A. niger growth inhibition at 0·2% and 72%P. italicum growth inhibition at 0·1%, respectively, and a delay of conidiation of 2 days compared with the control. In the antifungal activities of the microemulsion, GML and PS made major contributions with similar antifungal activities at a GML/PS weight ratio of 1: 3·5. Conclusions:  Food‐grade dilution‐stable microemulsions prepared with GML as oil phase for antifungal purpose are feasible and solubilization of a hydrotrope contributes to the formation of microemulsions and enhanced antifungal activities. Significance and Impact of the Study:  The present report represents the first to develop a food‐grade microemulsion system for antifugal purpose.