A strong conservative tendency in HBV transcriptase (RT): a majority of natural RT mutations derived from the S gene.

BACKGROUND & AIMS: Little is known about natural mutations in the HBV reverse transcriptase (RT) region. Our study aimed to characterize the natural RT mutation along the natural course of chronic Hepatitis B (CHB). METHODS: Sixty CHB patients (immune-tolerant phase, IT, n = 20; immune-active phase, IA, n = 20 and inactive carriers phase, IC, n = 20) were selected from the Focal study, including 25 subjects with median 18 months follow-up. Mutations were evaluated at both RT and main S protein encoding region by clone-based sequencing. RESULTS: The HBV RT quasispecies had significant lower heterogeneity in IT than IA and IC phases (P < 0.05), but not between IA and IC phases (P > 0.05). Limited heterogeneity over time was further confirmed in a longitudinal study. Locations of RT mutations were primarily located in the interdomians and the lowest in functional domains in each phase. Mutations in human leukocyte antigen (HLA) I epitopes (IT, 0.95%; IA, 1.31%; IC, 1.28%, P < 0.05) and HLA II epitopes (IT, 0.70%; IA, 0.90%; IC, 1.45%, P < 0.01) varied significantly over time. More frequent mutations were detected in the ORF of S gene from the same clones (HBsAg vs. RT: IT, 75 vs. 45; IA, 83 vs. 64; IC, 80 vs. 65). The majority of RT mutations were shared with genetic changes in the main S gene. CONCLUSIONS: Our findings suggested that HBV RT showed a strong conservative tendency and a majority of their natural mutations were derived from the same genetic changes in the S gene.

Expansion of circulating TFH cells and their associated molecules: involvement in the immune landscape in patients with chronic HBV infection.

BACKGROUND: Blood CXCR5+CD4+ T cells are defined as circulating T follicular helper (TFH) cells, which is required for effective humoral immunity. This study aimed to investigate the role of circulating TFH cells in patients with chronic hepatitis B virus (CHB) infection. METHODS: The frequency and phenotype of circulating TFH cells were monitored by flow cytometry in CHB patients and in healthy controls (HC). The expression of BCL-6, IL-21, IL-4, CXCR5, and IL-6R mRNA was analyzed using real-time PCR. Serum HBsAg, HBeAg, HBeAb, HBV DNA loads, ALT and AST were determined. The potential association of the frequency of TFH cells and their surface markers with clinical parameters was assessed. RESULTS: The frequency of CXCR5+CD4+ T cells was increased in CHB patients and positively correlated with ALT and AST but not with HBV DNA loads. Moreover, an expansion of ICOS-, PD-1-, CD40L-, and IL-21R-expressing TFH cells occurred in CHB patients, but failed to correlate with ALT, AST and HBV DNA loads. Interestingly, the frequency of CXCR5+CD4+ T cells and ICOS+CXCR5+CD4+ T cells was significantly higher in HBeAg positive CHB patients than in HC. Additionally, the percentages of CXCR5+CD4+ T cells were positively correlated with AST, and ICOS-expressing CXCR5+CD4+ T cells were negatively correlated with HBV DNA loads. No significant differences in the frequency of CXCR5+CD4+ T cells were observed between inactive carrier (IC) patients and healthy controls. However, ICOS-, PD-1-, CD40L-expressing TFH cells were increased in IC patients and positively correlated with AST. Furthermore, the expression of BCL-6, IL-21, IL-4, CXCR5, and IL-6R mRNA in TFH cells was higher in CHB patients than in HC. CONCLUSIONS: These data demonstrate that circulating TFH cells may participate in HBV-related immune responses. In addition to the frequency of TFH cells, the phenotype of these cells plays an important role in CHB patients.

Laparoscopic D2+ lymph node dissection in patients with obesity and gastric cancer: A retrospective study.

D2 lymph node dissection is widely used in laparoscopic radical gastrectomy for gastric cancer, and its efficacy and safety are known for patients with obesity. Currently, D2+ lymph node dissection is also applied to certain patients with gastric cancer of later stages. Due to the high difficulty of D2+ surgery, it is more challenging to perform on patients with obesity. There is currently limited research on the efficacy and safety of D2+ surgery in obese patients with gastric cancer. The present study aimed to retrospectively analyze the clinical data of patients undergoing laparoscopic radical gastrectomy for gastric cancer admitted to a single gastroenterology department. Patients with a body mass index ≥25 kg/m2 were included in the study. A total of 149 patients were selected as the research subjects and divided into two groups. The observation group comprised 74 patients who underwent D2+ lymph node dissection, while the control group comprised 75 patients who underwent standard D2 lymph node dissection. The surgical performance, postoperative recovery and postoperative complications of the two groups were compared. The results showed that the rates of conversion to open surgery in the D2+ and D2 groups were 5.4% (4/74) and 2.7% (2/75), respectively, and were not significantly different. The duration of surgery in the D2+ group (282.55±23.02 min) was significantly longer than that in the D2 group (271.45±20.05 min). The mean number of lymph node dissections in the D2+ group was 28.57±7.19, which was significantly higher than that in the D2 group (25.29±6.41). No statistically significant differences in intraoperative blood loss, time to first flatus, postoperative hospitalization days, total hospitalization expenses or postoperative complications was detected between the two groups. There were no deaths in either group within the 30-day perioperative period. In addition, there was no significant difference in the 3-year overall survival rate between the two groups, while the 5-year overall survival rate of the D2+ group was significantly higher than that of the D2 group. For obese patients with gastric cancer, D2+ surgery may increase the duration of surgery and slightly increase intraoperative blood loss compared with standard D2 radical surgery, but does not increase the incidence of postoperative complications. Moreover, D2+ surgery increases the number of lymph node dissections and improves the 5-year survival rate of patients. Therefore, it may be concluded that laparoscopic D2+ lymph node dissection is safe and feasible for obese patients with gastric cancer.

Surface fractures in pre-crystallized and crystallized zirconia-containing lithium silicate glass-ceramics generated in ultrasonic vibration-assisted machining.

Machining-induced surface fractures in ceramic restorations is a long-standing problem in dentistry, affecting the restorations' functionality and reliability. This study approached a novel ultrasonic vibration-assisted machining technique to zirconia-containing lithium silicate glass-ceramics (ZLS) and characterized its induced surface fracture topographies and morphologies to understand the microstructure-property-processing relations. The materials were processed using a digitally controlled ultrasonic milling machine at a harmonic vibration frequency with different amplitudes. Machining-induced surface fracture topographies were measured with a 3D white light optical profilometer using the arithmetic mean, peak and valley, and maximum heights, as well as the kurtosis and skewness height distributions, and the texture aspect ratios. Fracture morphologies were analysed using scanning electron microscopy (SEM). The surface fracture topographies were significantly dependent on the material microstructure, the mechanical properties, and the ultrasonic machining vibration amplitudes. Larger scale fractures with higher arithmetic mean, peak and valley heights, and kurtosis and skewness height distributions were induced in higher brittleness indexed pre-crystallized ZLS than lower indexed crystallized ZLS by conventional machining. Conchoidal fractures occurred in pre-crystallized ZLS while microcracks were found in crystallized state although brittle fractures mixed with localized ductile flow deformations dominated all machined ZLS surfaces. Ultrasonic machining at an ideal vibration amplitude resulted in more ductile removal, reducing fractured-induced peaks and valleys for both materials than conventional processing. This research demonstrates the microstructure-property-processing interdependence for ZLS materials and the novel machining technique to be superior to current processing, reducing fractures in the materials and potentially advancing dental CAD/CAM techniques.

Soft machining-induced surface and edge chipping damage in pre-crystalized lithium silicate glass ceramics.

Soft machining is a key procedure in fabrication of high-strength lithium-based silicate glass ceramic (LS) restorations. This paper reports on the diamond machining-induced surface and edge chipping damage in two pre-crystalized LS materials: pre-crystallized lithium metasilicate/orthophosphate glass ceramic (Pre-LS, IPS e.max CAD) and pre-crystallized zirconia-containing lithium metasilicate glass ceramic (Pre-ZLS, Vita Suprinity). Indentation techniques were used to measure the material mechanical properties. Soft machining was conducted using a robotic controlled apparatus mimicking dental CAD/CAM machining processes at different removal rates and enabling in-process force measurement. Machined surface roughness was assessed using 3D confocal optical profilometry in terms of the average and maximum surface heights. Scanning electron microscopy was used to assess diamond tool and machined surface and edge morphology. Soft machining of both materials was dominated by brittle fracture mixed with localized ductile flow. However, the higher brittleness index of Pre-ZLS than Pre-LS yielded higher degrees of machining-induced conchoidal fractures in Pre-ZLS in comparison with irregular fractures in Pre-LS. Thus, much larger surface roughness and deeper edge chipping damage were produced in Pre-ZLS than Pre-LS. Machining forces for Pre-ZLS were significantly smaller than Pre-LS, due to the lower machinability index associated with a complex relation of the mechanical properties as well as less debris adhesion for Pre-ZLS than Pre-LS. Further, increased material removal rates resulted in significantly increased machining forces, maximum surface roughness and fracture, and edge chipping damage in both Pre-ZLS and Pre-LS materials. Therefore, optimization of soft machining processes needs to be practiced to achieve accepted surface and edge quality at balanced removal rates.

Spiradiclisliboensis (Rubiaceae), a new species from limestone mountain areas in Guizhou, China.

Spiradiclisliboensis L. Wu & W. J. Liu, a new species in tribe Ophiorrhizeae of Rubiaceae from limestone mountain areas of Guizhou, south-western China, is described and illustrated. It is similar to S.guangdongensis and S.jingxiensis, but differs from the latter two by the following traits: stipule triangular, inflorescence sessile or with peduncle up to 0.5 mm long, pedicel 0.8-2.2 mm long, corolla white, salverform, corolla tube 1.6-2.2 cm long, corolla tube of long-styled morph inside with a villous ring and stigmas positioned at the throat of the corolla tube. The conservation status is assessed as "Vulnerable" (VU) according to the IUCN Red List Categories and Criteria.

Design and evaluation of a novel anti-reflux biliary stent with cone spiral valve.

Endoscopic placement of biliary stent is a well-established palliative treatment for biliary obstruction. However, duodenobiliary reflux after stent placement has been a common problem which may lead to dreadful complications. This paper designed a novel anti-reflux biliary stent with a cone spiral valve. Fluid-Structure Interaction (FSI) simulations were established to evaluate the efficiency of the anti-reflux stent comparing with a clinically applied standard stent. According to the stress distribution of the valve, the fatigue performance in the stress concentration area was analyzed. The results show that when the antegrade flow through the valve, the cone spiral valve could stretch and open to realize adequate drainage under the normal physiological pressure of biliary tract; When the duodenal reflux through the valve, the valve would be compressed and close with a result of nearly zero at the outlet flow rate. Furthermore, the anti-reflux stent achieved improved radial mechanical performance with 2.7 times higher radial stiffness than standard stent. Finite element analysis (FEA) also indicates that compared with the standard stent, the addition of the anti-reflux valve had little negative effect on flexibility of the stent. Fatigue analysis results showed that the valve was reliable. This research provides the new stent with a cone spiral valve and proves that it is technically feasible and effective for preventing the duodenobiliary reflux while ensuring the antegrade bile flow without compromising the other biomechanical performances.

Machinability: Zirconia-reinforced lithium silicate glass ceramic versus lithium disilicate glass ceramic.

Diamond grinding used in dental adjustment of high-strength zirconia-reinforced lithium silicate glass ceramic (ZLS) and lithium disilicate glass ceramic (LDGC) is challenging in restorative dentistry. This study aimed to compare the machinability of ZLS and LDGC in diamond grinding in terms of machining forces and energy, debris, surface and edge chipping damage. Grinding experiments in simulation of dental adjustment were conducted using a computer-assisted high-speed dental handpiece and coarse diamond burs. A piezoelectric force dynamometer and a high-speed data acquisition system were used for on-processing monitoring for assessment of grinding forces and energy. Grinding debris and grinding-induced surface and edge chipping damage were examined using scanning electron microscopy. The results show that grinding of ZLS required higher tangential and normal forces and energy than LDGC (p < 0.05). ZLS was ranked the most difficult to machine among dental glass ceramics based on a machinability index associated with the material mechanical properties. The higher machinability indices of ZLS and LDGC pose a challenge for clinicians to conduct high-efficient material removal for dental adjustment and repair. Both ZLS and LDGC debris were micro fractured particles but the former were smaller than the latter due to the finer microstructure of ZLS. Ground ZLS surfaces contained more irregular microchipping and microfracture in comparison with LDGC surfaces with intergranular fracture or grain dislodgement. Grinding-induced edge chipping damage remained a serious issue for both ZLS and LDGC, which depths ranged approximately 20-100 µm and significantly increased with the material removal rate (p < 0.01). As the zirconia-reinforcement in ZLS only slightly reduced edge chipping damage (p > 0.05), continued efforts are required to explore new reinforcement technologies for optimized LDGC.

Subsurface damage induced in dental resurfacing of a feldspar porcelain with coarse diamond burs.

The primary cause for early failure of ceramic restorations is surface and subsurface damage induced in adjustment and resurfacing using dental handpieces/burs. This paper reports finite element analysis (FEA) modelling of dental resurfacing to predict the degrees of subsurface damage, in combination with experimental measurement using scanning electron microscopy (SEM). The FEA predictions of subsurface damage induced in a feldspar porcelain with coarse diamond burs were in agreement with the SEM experimental measurement. These findings provide dental clinicians a quantitative description of the response of dental resurfacing-induced subsurface damage. The implication of the results for non-destructive evaluation of subsurface damage by FEA modelling will be practically meaningful to clinical dental restorations for high-quality ceramic restorations.

In-process assessment of dental cutting of a leucite-reinforced glass-ceramic.

This paper reports an in-process assessment of the dental cutting of a leucite-reinforced glass-ceramic with a high-speed dental handpiece under clinical operating conditions. The dental cutting was performed using a computer-controlled 2-degrees-of-freedom (2-DOF) testing regime and a coarse diamond bur of 106-125 microm grit size. Dynamic forces were monitored during the cutting process using a piezoelectric force dynamometer and a data acquisition system in both time and frequency domains. Bur speeds were found to decrease with the depth of cut and with the feed rate, by a maximum of 10.5% from the free-running speed of 322.2 krpm (1 krpm=1,000 rpm) to 288.4 krpm at the highest feed rate of 60mm/min and depth of cut of 50 microm. Both the tangential and normal forces increased with the depth of cut and the feed rate, in the ranges of 0.24-1.77 N and 0.60-2.93 N respectively. The torque increased with the depth of cut and feed rate. The specific cutting energy generally decreased with the depth of cut or the feed rate with the exception of a small-scale fluctuation at the higher depth of cut and feed rate. The dental cutting characteristics for the leucite glass-ceramic were similar to those for the feldspathic porcelain but had higher magnitudes.

Effects of microRNA-708 on Epithelial-Mesenchymal Transition, Cell Proliferation and Apoptosis in Melanoma Cells by Targeting LEF1 through the Wnt Signaling Pathway.

This study was conducted in order to elucidate the role microRNA-708 (miR-708) plays between proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) involving melanoma cells by targeting using LEF1 through the Wnt signaling pathway. Male Kunming mice were selected and subsequently divided into normal and model groups to take part in this study. Following cell line selection, the B16 cells with the highest miR-708 expression were selected and assigned into the control, blank, negative control (NC), miR-708 mimic, miR-708 inhibitor, siRNA-LEF1, and miR-708 inhibitor + siRNA-LEF1 groups. A Bioinformatics Web service and dual-luciferase reporter assay were conducted in order to determine the relationship between LEF1 and miR-708. The RT-qPCR method was performed in order to detect the miR-708 expression and mRNA expressions of LEF1, ß-catenin, Wnt3a, N-cadherin, Bcl-2, Bax, Caspase3, E-cadherin, and western blotting was used in order to detect the protein expressions of these genes. MTT assay, scratch test, Transwell assay, and flow cytometry were all conducted in order to detect the cell proliferation, migration, invasion, and cycle/apoptosis, respectively. LEF1 was verified as the target gene of miR-708. In comparison with the normal group, the model group had reduced expressions of miR-708, Bax, Caspase3, and E-cadherin, while showing elevated expressions of LEF1, ß-catenin, Bcl-2, Wnt3a, and N-cadherin. In comparison to the blank and control groups, the miR-708, mimic, and siRNA-LEF1 groups had elevated expressions of Bax, Caspase3, and E-cadherin, while also showing enhanced cell apoptosis. The miR-708, mimic, and siRNA-LEF1 groups also had decreased expressions of LEF1, ß-catenin, Bcl-2, Wnt3a, and N-cadherin, and reduced optical density value 48 h and 72 h after transfection. Besides, these two groups showed declined cell migration and invasion, as well as lengthened G0/G1 phase (increased cell number) and shortened S phase (decreased cell number). Our findings demonstrated that an overexpressed miR-708 inhibits the proliferation, invasion, migration, and EMT, but also promotes the apoptosis of melanoma cells by targeting LEF1 through the suppression of the Wnt signaling pathway.

In vitro rapid intraoral adjustment of porcelain prostheses using a high-speed dental handpiece.

In vitro rapid intraoral adjustment of porcelain prostheses was conducted using a high-speed dental handpiece and diamond bur. The adjustment process was characterized by measurement of removal forces and energy, with scanning electron microscopic (SEM) observation of porcelain debris, surfaces and subsurface damage produced as a function of operational feed rate. Finite element analysis (FEA) was applied to evaluate subsurface stress distributions and degrees of subsurface damage. The results show that an increase in feed rate resulted in increases in both tangential and normal forces (analysis of variance (ANOVA), P<0.01). When the feed rate approached the highest rate of 60mm min(-1) at a fixed depth of cut of 100microm, the tangential force was nearly seven times that at the lowest feed rate of 15mm min(-1). Consequently, the specific removal energy increased significantly (ANOVA, P<0.01), and the maximum depth of subsurface damage obtained was approximately 110 and 120microm at the highest feed rate of 60mm min(-1) using SEM and FEA, respectively. The topographies of both the adjusted porcelain surfaces and the debris demonstrate microscopically that porcelain was removed via brittle fracture and plastic deformation. Clinicians must be cautious when pursuing rapid dental adjustments, because high operational energy, larger forces and severe surface and subsurface damage can be induced.

Long-term study of male rabbit urethral mucosa reconstruction using epidermal cell.

AIM: To investigate the transformation of characteristics of epidermal cells from foreskin which were used to reconstruct male rabbit anterior urethra in combination with acellular collagen matrices. METHODS: In three rabbits, autologous foreskin epidermal cells were isolated, expanded in vitro, and seeded (inoculated) onto a tubular acellular collagen matrix, acquired from allogeneic rabbit bladder submucosa. A urethral mucosal defect was created, and urethral reconstruction was performed with the tubular acellular collagen matrix seeded with epidermal cells. RESULTS: On gross examination at 12 months following the procedure, the mucosa of the urethral grafts appeared lubricous and smooth. Urethrography showed that a wide urethral caliber had been maintained without any sign of strictures. Histological examination showed a transitional cell layer in the graft without evidence of a margin between the graft and the host tissue at 12 months postoperatively. CONCLUSION: Epidermal cells seeded onto acellular collagen matrices can be successfully used to reconstruct urethras that have defects and are transformed to transitional epithelial cells.

Micro-fine finishing of a feldspar porcelain for dental prostheses.

Intraoral adjustment of ceramic prostheses involving micro-finishing using diamond burs is a critical procedure in restorative dentistry because the durability of a restoration depends on the finishing process and quality. Force, energy and surface integrity in micro-fine finishing of a feldspar porcelain versus operational parameters were investigated using a 2-DOF (two-degrees-of-freedom) high-speed dental handpiece and a fine diamond bur of 20-30 microm grits. The tangential and normal forces were measured as being significantly small in the ranges 0.18-0.35 N and 0.22-0.59 N, respectively. High specific finishing energy of 110-2523J/mm(3) was observed in material removal, particularly when decreasing either the depth of cut or the feed rate. Scanning electron microscopy observations indicated that the surfaces generated were mainly due to ductile flow; however, microfractures also occurred in porcelain. Surface roughness was measured as 0.43-0.74 microm in terms of arithmetic mean value (R(a)), decreasing with the depth of cut, but insignificantly changing with the feed rate (ANOVA, P>0.05). Recommendations for clinical practice are made on the basis of our testing results.

A review of engineered zirconia surfaces in biomedical applications.

Zirconia is widely used for load-bearing functional structures in medicine and dentistry. The quality of engineered zirconia surfaces determines not only the fracture and fatigue behaviour but also the low temperature degradation (ageing sensitivity), bacterial colonization and bonding strength of zirconia devices. This paper reviews the current manufacturing techniques for fabrication of zirconia surfaces in biomedical applications, particularly, in tooth and joint replacements, and influences of the zirconia surface quality on their functional behaviours. It discusses emerging manufacturing techniques and challenges for fabrication of zirconia surfaces in biomedical applications.

Fracture, roughness and phase transformation in CAD/CAM milling and subsequent surface treatments of lithium metasilicate/disilicate glass-ceramics.

This paper studied surface fracture, roughness and morphology, phase transformations, and material removal mechanisms of lithium metasilicate/disilicate glass ceramics (LMGC/LDGC) in CAD/CAM-milling and subsequent surface treatments. LMGC (IPS e.max CAD) blocks were milled using a chairside dental CAD/CAM milling unit and then treated in sintering, polishing and glazing processes. X-ray diffraction was performed on all processed surfaces. Scanning electron microscopy (SEM) was applied to analyse surface fracture and morphology. Surface roughness was quantitatively characterized by the arithmetic average surface roughness Ra and the maximum roughness Rz using desktop SEM-assisted morphology analytical software. The CAD/CAM milling induced extensive brittle cracks and crystal pulverization on LMGC surfaces, which indicate that the dominant removal mechanism was the fracture mode. Polishing and sintering of the milled LMGC lowered the surface roughness (ANOVA, p < 0.05), respectively, while sintering also fully transformed the weak LMGC to the strong LDGC. However, polishing and glazing of LDGC did not significantly improve the roughness (ANOVA, p > 0.05). In comparison of all applied fabrication process routes, it is found that CAD/CAM milling followed by polishing and sintering produced the smoothest surface with Ra = 0.12 ± 0.08µm and Rz = 0.89 ± 0.26µm. Thus, it is proposed as the optimized process route for LMGC/LDGC in dental restorations. This route enables to manufacture LMGC/LDGC restorations with cost effectiveness, time efficiency, and improved surface quality for better occlusal functions and reduced bacterial plaque accumulation.

Surface quality of yttria-stabilized tetragonal zirconia polycrystal in CAD/CAM milling, sintering, polishing and sandblasting processes.

This paper studied the surface quality (damage, morphology, and phase transformation) of yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) in CAD/CAM milling, and subsequent polishing, sintering and sandblasting processes applied in dental restorations. X-ray diffraction and scanning electron microscopy (SEM) were used to scan all processed surfaces to determine phase transformations and analyse surface damage morphology, respectively. The average surface roughness (Ra) and maximum roughness (Rz) for all processed surfaces were measured using desk-top SEM-assisted morphology analytical software. X-ray diffraction patterns prove the sintering-induced monoclinic-tetragonal phase transformation while the sandblasting-induced phase transformation was not detected. The CAD/CAM milling of pre-sintered Y-TZP produced very rough surfaces with extensive fractures and cracks. Simply polishing or sintering of milled pre-sintered surfaces did not significantly improve their surface roughness (ANOVA, p>0.05). Neither sintering-polishing of the milled surfaces could effectively improve the surface roughness (ANOVA, p>0.05). The best surface morphology was produced in the milling-polishing-sintering process, achieving Ra=0.21±0.03µm and Rz=1.73±0.04µm, which meets the threshold for bacterial retention. Sandblasting of intaglios with smaller abrasives was recommended as larger abrasive produced visible surface defects. This study provides technical insights into process selection for Y-TZP to achieve the improved restorative quality.

Machinability of lithium disilicate glass ceramic in in vitro dental diamond bur adjusting process.

Esthetic high-strength lithium disilicate glass ceramics (LDGC) are used for monolithic crowns and bridges produced in dental CAD/CAM and oral adjusting processes, which machinability affects the restorative quality. A machinability study has been made in the simulated oral clinical machining of LDGC with a dental handpiece and diamond burs, regarding the diamond tool wear and chip control, machining forces and energy, surface finish and integrity. Machining forces, speeds and energy in in vitro dental adjusting of LDGC were measured by a high-speed data acquisition and force sensor system. Machined LDGC surfaces were assessed using three-dimensional non-contact chromatic confocal optical profilometry and scanning electron microscopy (SEM). Diamond bur morphology and LDGC chip shapes were also examined using SEM. Minimum tool wear but significant LDGC chip accumulations were found. Machining forces and energy significantly depended on machining conditions (p<0.05) and were significantly higher than other glass ceramics (p<0.05). Machining speeds dropped more rapidly with increased removal rates than other glass ceramics (p<0.05). Two material machinability indices associated with the hardness, Young's modulus and fracture toughness were derived based on the normal force-removal rate relations, which ranked LDGC the most difficult to machine among glass ceramics. Surface roughness for machined LDGC was comparable for other glass ceramics. The removal mechanisms of LDGC were dominated by penetration-induced brittle fracture and shear-induced plastic deformation. Unlike most other glass ceramics, distinct intergranular and transgranular fractures of lithium disilicate crystals were found in LDGC. This research provides the fundamental data for dental clinicians on the machinability of LDGC in intraoral adjustments.

Activation of intrahepatic CD4+CXCR5+ T and CD19+ B cells is associated with viral clearance in a mouse model of acute hepatitis B virus infection.

The role of immunity in the pathogenesis of acute hepatitis B virus (HBV) infection is poorly understood. The purpose of this research was to define the intrahepatic immune factors responsible for viral clearance during acute HBV infection. The model of acute HBV infection was established by hydrodynamically transfecting mice with pCDNA3.1-HBV1.3 plasmids which contained a supergenomic HBV1.3-length transgene. The frequency of CD4+ CXCR5+ T cells, CD19+ B cells and their surface molecules in livers, spleens and peripheral blood were detected using flow cytometry. The lymphomononuclear cells isolated from the livers of transfected mice were further stimulated by HBc-derived peptides and then the frequency and cytokine secretion of HBV-specific CD4+CXCR5+ T cells were detected. We found that the frequency of CXCR5+ in CD4+ T cells was specifically increased; the expression of PD-1 was decreased while the expression of ICOS was increased on intrahepatic CD4+CXCR5+ T cells. Although the frequency of CD19+ B cells was not affected, the expression of PDL-1, ICOSL and IL-21R on B cells was increased in the livers of mice. The frequency of HBV-specific CD4+CXCR5+ T cells and the production of IL-21 by intrahepatic CD4+CXCR5+ T cells of mice with acute HBV infection were increased after stimulation. Furthermore, the expression of function-related molecules of intrahepatic CD4+CXCR5+ T, including Bcl-6, CXCR5, IL-6, IL-6R, IL-21 and IL-4 in the liver was increased during acute HBV infection. In conclusion, the activation of intrahepatic CD4+CXCR5+ T cells and B cells was associated with the clearance of HBV during acute infection.

Quantitative assessment of the enamel machinability in tooth preparation with dental diamond burs.

Enamel cutting using dental handpieces is a critical process in tooth preparation for dental restorations and treatment but the machinability of enamel is poorly understood. This paper reports on the first quantitative assessment of the enamel machinability using computer-assisted numerical control, high-speed data acquisition, and force sensing systems. The enamel machinability in terms of cutting forces, force ratio, cutting torque, cutting speed and specific cutting energy were characterized in relation to enamel surface orientation, specific material removal rate and diamond bur grit size. The results show that enamel surface orientation, specific material removal rate and diamond bur grit size critically affected the enamel cutting capability. Cutting buccal/lingual surfaces resulted in significantly higher tangential and normal forces, torques and specific energy (p<0.05) but lower cutting speeds than occlusal surfaces (p<0.05). Increasing material removal rate for high cutting efficiencies using coarse burs yielded remarkable rises in cutting forces and torque (p<0.05) but significant reductions in cutting speed and specific cutting energy (p<0.05). In particular, great variations in cutting forces, torques and specific energy were observed at the specific material removal rate of 3mm(3)/min/mm using coarse burs, indicating the cutting limit. This work provides fundamental data and the scientific understanding of the enamel machinability for clinical dental practice.