Persistent Loss of Hepatitis B Virus Markers in Serum without Cellular Immunity by Combination of Peginterferon and Entecavir Therapy in Humanized Mice.

Nucleot(s)ide analogues and peginterferon (PEG-IFN) treatment are the only approved therapies for chronic hepatitis B virus (HBV) infection. However, complete eradication of the virus, as indicated by persistent loss of hepatitis B surface antigen (HBsAg), is rare among treated patients. This is due to long-term persistence of the HBV genome in infected hepatocytes in the form of covalently closed circular DNA (cccDNA). In this study, we investigated whether administration of a large dose of a nucleoside analogue in combination with PEG-IFN can achieve long-term loss of HBsAg in human hepatocyte chimeric mice. Mice were treated with a high dose of entecavir and/or PEG-IFN for 6 weeks. High-dose combination therapy with both drugs resulted in persistently negative HBV DNA in serum. Although small amounts of HBV DNA and cccDNA (0.1 and 0.01 copy/cell, respectively) remained in the mouse livers, some of the mice remained persistently negative for serum HBV DNA at 13 weeks after cessation of the therapy. Serum HBsAg and hepatitis B core-related antigen (HBcrAg) continued to decrease and eventually became negative at 12 weeks after cessation of the therapy. Analysis of the HBV genome in treated mice showed accumulation of G-to-A hypermutation and CpG III island methylation. Persistent loss of serum HBV DNA and loss of HBV markers by high-dose entecavir and PEG-IFN combination treatment in chimeric mice suggests that control of HBV can be achieved even in the absence of a cellular immune response.

A novel approach to full-mouth rehabilitation of dentinogenesis imperfecta type II: Case series with review of literature.

RATIONALE: Dentinogenesis imperfecta (DI) is an autosomal-dominant disorder. The most common clinical manifestations, including obliterated tooth tissues and severe tooth wear, usually lead to tooth extractions. It remains a great challenge for dentists to preserve the residual tooth tissue and establish the esthetics and occlusion of dentitions. PATIENTS CONCERNS: 25-year-old twin sisters, who had suffered from dentinogenesis imperfecta type II for more than 10 years, presented with continuous tooth wear and discomfort from wearing a removable partial denture for more than 3 years. DIAGNOSIS: Intraoral examination showed extensive tooth wear with enamel exfoliation and typical amber-brown color with an opalescent discoloration. Their panoramic radiographs revealed completely obliterated tooth tissues and severe tooth wear. INTERVENTIONS AND OUTCOMES: The dentitions were restored with post-and-core crowns and pin lays after preparing root post paths and pin holes guided by computer-aided design/computer-aided manufacturing (CAD/CAM) procedures, resulting in a successful repair. LESSONS: Severe tooth wear and tooth tissue obliteration are typical clinical manifestations in DI-affected dentitions, increasing the complexity and difficulty in dental restorations. Early diagnosis and appropriate treatments are essential to achieve a favorable prognosis. CAD/CAM procedures, permitting accurate and effective treatment, possess promising potential in the treatment of DI-affected dentitions.

Intrafibrillar mineralization of type I collagen with calcium carbonate and strontium carbonate induced by polyelectrolyte-cation complexes.

Calcium carbonate (CaCO3), possessing excellent biocompatibility, bioactivity, osteoconductivity and superior biodegradability, may serve as an alternative to hydroxyapatite (HAp), the natural inorganic component of bone and dentin. Intrafibrillar mineralization of collagen with CaCO3 was achieved through the polymer-induced liquid precursor (PILP) process for at least 2 days. This study aims to propose a novel pathway for rapid intrafibrillar mineralization with CaCO3 by sequential application of the carbonate-bicarbonate buffer and polyaspartic acid (pAsp)-Ca suspension. Fourier transform infrared (FTIR) spectroscopy, zeta potential measurements, atomic force microscopy/Kelvin probe force microscopy (AFM/KPFM), and three-dimensional stochastic optical reconstruction microscopy (3D STORM) demonstrated that the carbonate-bicarbonate buffer significantly decreased the surface potential of collagen and CO32-/HCO3- ions could attach to collagen fibrils via hydrogen bonds. The electropositive pAsp-Ca complexes and free Ca2+ ions are attracted to and interact with CO32-/HCO3- ions through electrostatic attractions to form amorphous calcium carbonate that crystallizes gradually. Moreover, like CaCO3, strontium carbonate (SrCO3) can deposit inside the collagen fibrils through this pathway. The CaCO3-mineralized collagen gels exhibited better biocompatibility and cell proliferation ability than SrCO3. This study provides a feasible strategy for rapid collagen mineralization with CaCO3 and SrCO3, as well as elucidating the tissue engineering of CaCO3-based biomineralized materials.

STMP and PVPA as Templating Analogs of Noncollagenous Proteins Induce Intrafibrillar Mineralization of Type I Collagen via PCCP Process.

The phosphorylated noncollagenous proteins (NCPs) play a vital role in manipulating biomineralization, while the mechanism of phosphorylation of NCPs in intrafibrillar mineralization of collagen fibril has not been completely deciphered. Poly(vinylphosphonic acid) (PVPA) and sodium trimetaphosphate (STMP) as templating analogs of NCPs induce hierarchical mineralization in cooperation with indispensable sequestration analogs such as polyacrylic acid (PAA) via polymer-induced liquid-like precursor (PILP) process. Herein, STMP-Ca and PVPA-Ca complexes are proposed to achieve rapid intrafibrillar mineralization through polyelectrolyte-Ca complexes pre-precursor (PCCP) process. This strategy is further verified effectively for remineralization of demineralized dentin matrix both in vitro and in vivo. Although STMP micromolecule fails to stabilize amorphous calcium phosphate (ACP) precursor, STMP-Ca complexes facilely permeate into intrafibrillar interstices and trigger phase transition of ACP to hydroxyapatite within collagen. In contrast, PVPA-stabilized ACP precursors lack liquid-like characteristic and crystallize outside collagen due to rigid conformation of PVPA macromolecule, while PVPA-Ca complexes infiltrate into partial intrafibrillar intervals under electrostatic attraction and osmotic pressure as evidenced by intuitionistic 3D stochastic optical reconstruction microscopy (3D-STORM). The study not only extends the variety and size range of polyelectrolyte for PCCP process but also sheds light on the role of phosphorylation for NCPs in biomineralization.

Muscle Fatigue Sensor Based on Ti3 C2 Tx MXene Hydrogel.

MXene-based hydrogels have received significant attention due to several promising properties that distinguish them from conventional hydrogels. In this study, it is shown that both strain and pH level can be exploited to tune the electronic and ionic transport in MXene-based hydrogel (M-hydrogel), which consists of MXene (Ti3 C2 Tx )-polyacrylic acid/polyvinyl alcohol hydrogel. In particular, the strain applied to the M-hydrogel changes MXene sheet orientation which leads to modulation of ionic transport within the M-hydrogel, due to strain-induced orientation of the surface charge-guided ionic pathway. Simultaneously, the reorientation of MXene sheets under the axial strain increases the electronic resistance of the M-hydrogel due to the loss of the percolative network of conductive MXene sheets during the stretching process. The iontronic characteristics of the M-hydrogel can thus be tuned by strain and pH, which allows using the M-hydrogel as a muscle fatigue sensor during exercise. A fully functional M-hydrogel is developed for real-time measurement of muscle fatigue during exercise and coupled it to a smartphone to provide a portable or wearable digital readout. This concept can be extended to other fields that require accurate analysis of constantly changing physical and chemical conditions, such as physiological changes in the human body.

A Hydroxypropyl Methylcellulose Film Loaded with AFCP Nanoparticles for Inhibiting Formation of Enamel White Spot Lesions.

OBJECTIVE: This study investigated the effects of mineralizing film consisting of hydroxypropyl methylcellulose (HPMC) and amorphous fluorinated calcium phosphate (AFCP) nanoparticles on enamel white spot lesions (WSLs). MATERIAL AND METHODS: The AFCP nanoparticles and mineralizing film were prepared via nanoprecipitation and solvent evaporation, respectively. They were characterized with Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction (SAED), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), inductively coupled plasma atomic emission spectrometry (ICP-AES), and fluoride ion selective electrode. Thirty-two human enamel slices (4 mm × 4 mm × 1.5 mm) were highly polished and randomly assigned to four groups: negative control (no treatment); pure HPMC film; mineralizing film; GC Tooth Mousse Plus® (contains 10% CPP-ACP and 0.2% NaF). Subsequently, samples were challenged by a modified pH-cycling and characterized by color measurement, Micro-CT, SEM/EDX, and nanoindentation. RESULTS: The mineralizing film could sustain release of Ca, P and F ions over 24 h and maintain AFCP nanoparticles in metastable state over 8~12 h. During 4 weeks of pH cycling, the mineralizing film group exhibited least color change (∆E), mineral loss and lesion depth (120 ± 10 µm) among four groups (p < 0.05). SEM findings revealed that the porosities among enamel crystals increased in negative control and pure HPMC film groups after pH cycling, whereas in mineralizing film group, the original microstructure of enamel was well conserved and mineral deposits were detected between enamel prisms. Mineralizing film group demonstrated a least reduction of nanomechanical properties such as elastic modulus of 77.02 ± 6.84 GPa and hardness of 3.62 ± 0.57 GPa (p < 0.05). CONCLUSION: The mineralizing film might be a promising strategy for prevention and management of WSLs via inhibiting enamel demineralization and promoting enamel remineralization.

The effect of prime-and-rinse approach using MDP micellar solutions on extrafibrillar demineralization and dentin bond performance.

OBJECTIVE: This study investigated the effects of prime-and-rinse approach using 10-methacryloyloxydecyl dihydrogen phosphate (MDP) micellar solutions on extrafibrillar demineralization and dentin bond performance of etch-and-rinse adhesive. METHODS: The micellar solutions were prepared by adding 15% MDP in two ethanol-aqueous (75:25, 55:45 V/V%) solutions, referring to MDP/EtOH75 and MDP/EtOH55. After mid-coronal dentin surfaces were either etched (control) or conditioned with MDP/EtOH75 and MDP/EtOH55 and rinsed, they were applied with adhesive (Adpter Single Bond 2) in dry- or wet-bonding mode and placed with composite resin (Filtek Z350 XT). They were prepared into multiple micro-beams for micro-tensile bond strengths (MTBS) testing after storage in water for 24 h or subjecting to thermocycling. The other pretreated dentin surfaces were analyzed by TF-XRD, ATR-FTIR, HRTEM, FE-SEM, contact angle measurement and nanoindentation testing. The MTBS data was analyzed with two-way ANOVA followed by LSD post-hoc test. RESULTS: MDP/EtOH75 produced significantly greater MTBS values than MDP/EtOH55 and control after thermocycling aging in dry- or wet-bonding mode (P < 0.05). The ATR-FTIR spectrums shows that ratios of phosphate/monomer (1,034 cm-1/1,716 cm-1) on MDP/EtOH75-, MDP/EtOH55-treated dentin surfaces are 0.51 and 0.23, respectively. This is confirmed by HRTEM images and SAED pattern that intrafibrillar minerals were mostly preserved after treatment with MDP/EtOH75. MDP/EtOH75 produced significantly higher elastic modulus and nanohardness on pretreated dentin surface than MDP/EtOH55 (P < 0.05). TF-XRD pattern shows some MDP-Ca salts remained on the primed dentin surface. SIGNIFICANCE: Prime-and-rinse approach using MDP/EtOH75 micellar solution could produce mostly extrafibrillar demineralization, and greatly increase dentin bond durability in dry- or wet-bonding mode.

A flexible pressure sensor based on rGO/polyaniline wrapped sponge with tunable sensitivity for human motion detection.

High-performance stretchable and wearable electronic skins (E-skins) with high sensitivity and a large sensing range are urgently required with the rapid development of the Internet of things and artificial intelligence. Herein, a reduced graphene oxide (rGO)/polyaniline wrapped sponge is prepared via rGO coating and the in situ synthesis of polyaniline nanowires (PANI NWs) on the backbones of sponge for the fabrication of pressure sensors. From the as-prepared flexible sensor, tunable sensitivity (0.042 to 0.152 kPa-1), wide working range (0-27 kPa), fast response (∼96 ms), high current output (∼300 µA at 1 V), frequency-dependent performance reliable repeatability (∼9000 cycle) and stable signal waveform output can be readily obtained. In addition to tiny physiological activities (voice recognition, swallowing, mouth opening, blowing and breath), robust human motions (finger bending, elbow movement and knee squatting-arising) can also be detected in real-time by the flexible sensors based on rGO/polyaniline wrapped sponge. All the results demonstrate that the flexible pressure sensor based on the functional-sponge is a promising candidate for healthcare monitoring and wearable circuitry in artificial intelligence.

IL28B polymorphism is associated with fatty change in the liver of chronic hepatitis C patients.

BACKGROUND: Several single nucleotide polymorphisms (SNPs) within the interleukin 28B (IL28B) locus are associated with sustained viral response in chronic hepatitis C (HCV) patients who were treated with pegylated interferon (PEG-IFN) plus ribavirin (RBV) combination therapy. Recently, an association between γ-GTP level and IL28B genotype was identified. In this study, the relationship between IL28B genotype and liver steatosis was analyzed. METHODS: One hundred fifty-three patients who underwent liver biopsy before PEG-IFN plus RBV combination therapy were enrolled. The level of liver steatosis was measured using a BIOREVO BZ-9000 microscope, and the proportion of fatty change and clear cell change were calculated using Dynamic cell count BZ-H1C software. IL28B SNP genotype (rs8099917) was determined using the Invader Assay. RESULTS: Vesicular change was significantly associated with body mass index (BMI), HCV RNA titer, serum aspartate aminotransferase, γ-GTP, IL28B genotype and liver fibrosis level (P < 0.05). Clear cell change was significantly associated with serum aspartate aminotransferase, γ-GTP and IL28B genotype by univariate logistic regression analysis (P < 0.05). Under multiple logistic regression, IL28B genotype (OR(adj) = 8.158; 95% CI 2.412-27.589), liver fibrosis (OR(adj) = 2.541; 95% CI 1.040-6.207) and BMI (OR(adj) = 1.147; 95% CI 1.011-1.301) were significant independent factors for vesicular change and IL28B genotype (OR(adj) = 3.000; 95% CI 1.282-7.019) for clear cell change. CONCLUSION: In this study, a new quantitative method to objectively evaluate hepatic steatosis was described. IL28B genotypes were significantly associated with both vesicular and clear cell changes of livers in chronic hepatitis C patients.