Intranasal HBsAg/HBcAg-Containing Vaccine Induces Neutralizing Anti-HBs Production in Hepatitis B Vaccine Non-Responders.

Hepatitis B vaccine induces the production of antibodies against hepatitis B surface antigen (anti-HBs) and prevents hepatitis B virus (HBV) infection. However, 5-10% of individuals cannot develop anti-HBs even after multiple vaccinations (HB vaccine non-responders). We developed an intranasal vaccine containing both HBs antigen (HBsAg) and HB core antigen (HBcAg) and mixed it with a viscosity enhancer, carboxyl vinyl polymer (CVP-NASVAC). Here, we investigated the prophylactic capacity of CVP-NASVAC in HB vaccine non-responders. Thirty-four HB vaccine non-responders were administered three doses of intranasal CVP-NASVAC. The prophylactic capacity of CVP-NASVAC was assessed by evaluating the induction of anti-HBs and anti-HBc (IgA and IgG) production, HBV-neutralization activity of sera, and induction of HBs- and HBc-specific cytotoxic T lymphocytes (CTLs). After CVP-NASVAC administration, anti-HBs and anti-HBc production were induced in 31/34 and 27/34 patients, respectively. IgA anti-HBs and anti-HBc titers significantly increased after CVP-NASVAC vaccination. HBV-neutralizing activity in vitro was confirmed in the sera of 26/29 CVP-NASVAC-administered participants. HBs- and HBc-specific CTL counts substantially increased after the CVP-NASVAC administration. Mild adverse events were observed in 9/34 participants; no serious adverse events were reported. Thus, CVP-NASVAC could be a beneficial vaccine for HB vaccine non-responders.

Application of spatial transcriptomics analysis using the Visium system for the mouse nasal cavity after intranasal vaccination.

Intranasal vaccines that elicit mucosal immunity are deemed effective against respiratory tract infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but their ability to induce humoral immunity characterized by immunoglobulin A (IgA) and IgG production is low. It has been reported that vaccination with a mixture of a viscous base carboxyvinyl polymer (CVP) and viral antigens induced robust systemic and mucosal immune responses. In this study, we analyzed the behavior of immunocompetent cells in the nasal cavity over time by spatial transcriptome profiling induced immediately after antigen vaccination using CVP. We established a method for performing spatial transcriptomics using the Visium system in the mouse nasal cavity and analyzed gene expression profiles within the nasal cavity after intranasal vaccination. Glycoprotein 2 (Gp2)-, SRY-box transcription factor 8 (Sox8)-, or Spi-B transcription factor (Spib)-expressing cells were increased in the nasal passage (NP) region at 3-6 hr after SARS-CoV-2 spike protein and CVP (S-CVP) vaccination. The results suggested that microfold (M) cells are activated within a short period of time (3-6 hr). Subsequent cluster analysis of cells in the nasal cavity showed an increase in Cluster 9 at 3-6 hr after intranasal vaccination with the S-CVP. We found that Il6 in Cluster 9 had the highest log2 fold values within the NP at 3-6 hr. A search for gene expression patterns similar to that of Il6 revealed that the log2 fold values of Edn2, Ccl20, and Hk2 also increased in the nasal cavity after 3-6 hr. The results showed that the early response of immune cells occurred immediately after intranasal vaccination. In this study, we identified changes in gene expression that contribute to the activation of M cells and immunocompetent cells after intranasal vaccination of mice with antigen-CVP using a time-series analysis of spatial transcriptomics data. The results facilitated the identification of the cell types that are activated during the initial induction of nasal mucosal immunity.

Biodistribution assessment of cationic pullulan nanogel, a nasal vaccine delivery system, in mice and non-human primates.

Cationic cholesteryl-group-bearing pullulan nanogel (cCHP-nanogel) is an effective drug-delivery system for nasal vaccines. However, cCHP-nanogel-based nasal vaccines might access the central nervous system due to its close proximity via the olfactory bulb in the nasal cavity. Using real-time quantitative tracking of the nanogel-based nasal botulinum neurotoxin and pneumococcal vaccines, we previously confirmed the lack of deposition of vaccine antigen in the cerebrum or olfactory bulbs of mice and non-human primates (NHPs), rhesus macaques. Here, we used positron emission tomography to investigate the biodistribution of the drug-delivery system itself, cCHP-nanogel after mice and NHPs were nasally administered with 18F-labeled cCHP nanogel. The results generated by the PET analysis of rhesus macaques were consistent with the direct counting of radioactivity due to 18F or 111In in dissected mouse tissues. Thus, no depositions of cCHP-nanogel were noted in the cerebrum, olfactory bulbs, or eyes of both species after nasal administration of the radiolabeled cCHP-nanogel compound. Our findings confirm the safe biodistribution of the cCHP-nanogel-based nasal vaccine delivery system in mice and NHPs.

Klotho Supplementation Reverses Renal Dysfunction and Interstitial Fibrosis in Remnant Kidney.

INTRODUCTION: While recent investigations show that klotho exerts renoprotective actions, it has not been fully addressed whether klotho protein supplementation reverses renal damage. METHODS: The impacts of subcutaneous klotho supplementation on rats with subtotal nephrectomy were examined. Animals were divided into 3 groups: group 1 (short remnant [SR]): remnant kidney for 4 weeks, group 2 (long remnant [LR]): remnant kidney for 12 weeks, and group 3 (klotho supplementation [KL]): klotho protein (20 µg/kg/day) supplementation on the remnant kidney. Blood pressure, blood and urine compositions with conventional methods such as enzyme-linked immunosorbent assay and radioimmunoassay, kidney histology, and renal expressions of various genes were analyzed. In vitro studies were also performed to support in vivo findings. RESULTS: Klotho protein supplementation decreased albuminuria (-43%), systolic blood pressure (-16%), fibroblast growth factor (FGF) 23 (-51%) and serum phosphate levels (-19%), renal angiotensin II concentration (-43%), fibrosis index (-70%), renal expressions of collagen I (-55%), and transforming growth factor ß (-59%) (p < 0.05 for all). Klotho supplementation enhanced fractional excretion of phosphate (+45%), glomerular filtration rate (+76%), renal expressions of klotho (+148%), superoxide dismutase (+124%), and bone morphogenetic protein (BMP) 7 (+174%) (p < 0.05 for all). CONCLUSION: Our data indicated that klotho protein supplementation inactivated renal renin-angiotensin system, reducing blood pressure and albuminuria in remnant kidney. Furthermore, exogenous klotho protein supplementation elevated endogenous klotho expression to increase phosphate excretion with resultant reductions in FGF23 and serum phosphate. Finally, klotho supplementation reversed renal dysfunction and fibrosis in association with improved BMP7 in remnant kidney.

Direct Quantification of Attogram Levels of Strontium-90 in Microscale Biosamples Using Isotope Dilution-Thermal Ionization Mass Spectrometry Assisted by Quadrupole Energy Filtering.

Although thermal ionization mass spectrometry (TIMS) has been employed for the high-precision analysis of isotope ratios, direct quantification of artificial mono-nuclide in the environment is difficult by even using isotope dilution (ID) due to the coexistence of the great magnitude of natural stable nuclides or isobars. In traditional TIMS and ID-TIMS, a sufficient amount of stable Sr doped on a filament is required to realize a stable and adequate ion-beam intensity (i.e., thermally ionized beams). However, the background noise (BGN) at m/z 90, detected by an electron multiplier, disturbs 90Sr analysis at low concentration levels due to peak tailing of a significant 88Sr ion beam dependent on the 88Sr-doping amount. Here, TIMS assisted by quadruple energy filtering was successfully employed for the direct quantification of attogram levels of an artificial monoisotopic radionuclide strontium-90 (90Sr) in microscale biosamples. Direct quantification was achieved by integrating the ID quantification of natural Sr and simultaneous 90Sr/86Sr isotope ratio analysis. Additionally, the measurement amount calculated by the combination of the ID and intercalibration was corrected for the net result amount of 90Sr by subtracting dark noise and the detected amount derived from the survived 88Sr, which are equivalent with the BGN intensity at m/z 90. Background correction revealed that the detection limits were in the range of 6.15 × 10-2-3.90 × 10-1 ag (0.31-1.95 µBq), depending on the concentration of natural Sr in a 1 µL sample, and the quantification of 0.98 ag (5.0 µBq) of 90Sr in 0-300 mg/L of natural Sr was successful. This method could analyze small sample quantities (1 µL), and the quantitative results were verified against authorized radiometric analysis techniques. Furthermore, the amount of 90Sr in actual teeth was successfully quantified. This method will be a powerful tool for measuring 90Sr in the measurement of micro-samples, which are required to assess and understand the degree of internal radiation exposure.

Intranasal therapeutic vaccine containing HBsAg and HBcAg for patients with chronic hepatitis B; 18 months follow-up results of phase IIa clinical study.

AIMS: HBsAg loss with anti-HBs acquisition is considered a functional cure and ideal treatment goal for patients with CHB. Our group have reported the efficacy of therapeutic vaccine with HBsAg and HBcAg (NASVAC) by intranasal and subcutaneous injection. In this study, we investigated the safety and efficacy of newly developed CVP-NASVAC, which contained NASVAC with mucoadhesive carboxyl vinyl polymer (CVP) in the dedicated device. METHODS: A single dose, open-label, phase IIa clinical trial of CVP-NASVAC was conducted. Patients with CHB treated with nucleoside/nucleotide analogs (NAs) and HBV carriers not undergoing anti-HBV treatment were enrolled. CVP-NASVAC was injected through the nose for, in total, 10 times. Participants were followed-up for 18 months, and their HBsAg reduction and anti-HBs induction assessed as endpoints. RESULTS: Among the patients with CHB treated with NAs (n = 27) and HBV carriers without NAs (n = 36), 74.1% and 75.0% exhibited reductions in their baseline HBsAg, and the mean reductions were -0.1454 log10  IU/ml (p < 0.05) and -0.2677 log10  IU/ml (p < 0.05), respectively. Anti-HBs antibody was detected in 40.7% and 58.3% of patients treated with and without NAs, respectively. Six of 71 (9.5%) patients were functionally cured after the CVP-NASVAC treatment. CONCLUSIONS: Anti-HBs induction and HBsAg reduction was observed after CVP-NASVAC treatment in some patients with CHB. The CVP-NASVAC is a safe treatment, which might expect to achieve functional cure for patients with CHB.

Identification of mechanics-responsive osteocyte signature in osteoarthritis subchondral bone.

AIMS: Osteoarthritis (OA) is a common degenerative joint disease. The osteocyte transcriptome is highly relevant to osteocyte biology. This study aimed to explore the osteocyte transcriptome in subchondral bone affected by OA. METHODS: Gene expression profiles of OA subchondral bone were used to identify disease-relevant genes and signalling pathways. RNA-sequencing data of a bone loading model were used to identify the loading-responsive gene set. Weighted gene co-expression network analysis (WGCNA) was employed to develop the osteocyte mechanics-responsive gene signature. RESULTS: A group of 77 persistent genes that are highly relevant to extracellular matrix (ECM) biology and bone remodelling signalling were identified in OA subchondral lesions. A loading responsive gene set, including 446 principal genes, was highly enriched in OA medial tibial plateaus compared to lateral tibial plateaus. Of this gene set, a total of 223 genes were identified as the main contributors that were strongly associated with osteocyte functions and signalling pathways, such as ECM modelling, axon guidance, Hippo, Wnt, and transforming growth factor beta (TGF-ß) signalling pathways. We limited the loading-responsive genes obtained via the osteocyte transcriptome signature to identify a subgroup of genes that are highly relevant to osteocytes, as the mechanics-responsive osteocyte signature in OA. Based on WGCNA, we found that this signature was highly co-expressed and identified three clusters, including early, late, and persistently responsive genes. CONCLUSION: In this study, we identified the mechanics-responsive osteocyte signature in OA-lesioned subchondral bone. Cite this article: Bone Joint Res 2022;11(6):362-370.

In vitro characterization of primary osteoblasts on titanium surfaces processed with wire-type electric discharge machining.

The fixation of titanium implants in bone tissue is affected by the presence of a passive titanium oxide (TiO2) layer. Specifically, oxidation products in the amorphous TiO2 matrix enhance the mechanical properties of mineralized tissues. In addition, in vitro mineralization mediated by primary osteoblasts on amorphous TiO2 generates stiff tissues in a process that resembles pathological mechanisms connected with tumors and proceeds through hydrogen peroxide-inducible clone-5 (Hic-5) expression. However, the relationship between surface-based peroxidation and stiff mineralized tissue formation remains unclear. In this study, titanium samples were processed using wire electrical discharge machining to generate oxidation products in amorphous TiO2. The gene expression profiles of primary osteoblasts cultured on these specimens were characterized. Increased expression of Hic-5 was correlated with the presence of peroxidation products. The crystallization of amorphous TiO2 in these samples reduced the expression of both Hic-5 and lysyl oxidase, an enzyme that promotes matrix cross-linking.

A part per trillion isotope ratio analysis of 90Sr/88Sr using energy-filtered thermal ionization mass spectrometry.

Strontium-90 is a major radioactive nuclide released by nuclear accidents and discharge waste. Input of such radioactive nuclide into earth surface environment causes potential threat of long-term internal exposure when taken up by organism. Rapid and precise measurement of 90Sr in variety of environmental sample is important to understand the distribution and dynamics of 90Sr in the local environment after the accident and to assess the effect of radioactive nuclide inputs on bodies. However, previous 90Sr measurement techniques have drawbacks such as long measurement times for radiometry and high detection limits for mass spectrometry. Here we present a technique to accurately measure a significantly small amount of 90Sr in natural environmental samples using an energy-filtered thermal ionization mass spectrometry. Our technique achieved a 90Sr detection limit of 0.23 ag, which corresponds to a 90Sr activity of 1.2 µBq. The detection limit was lowered by two orders of magnitude compared with the previous mass spectrometric 90Sr analyses. The ability of our technique will expand the applicability of mass spectrometric 90Sr survey not only to the rapid 90Sr survey upon nuclear accidents but also to study a long-term environmental diffusion of radioactive materials using size-limited environmental and biological samples.

Shear bond strength of an acrylic resin to a ceria-stabilized zirconia-alumina nanocomposite.

STATEMENT OF PROBLEM: Ceria-stabilized zirconia-alumina nanocomposite (Ce-TZP-Al2O3) has properties that may be suitable for partial denture frameworks. However, studies on its adhesion strength and durability with denture base resin are lacking. PURPOSE: The purpose of this in vitro study was to determine the optimal surface treatment for Ce-TZP-Al2O3 to secure a durable bond with an acrylic resin. MATERIAL AND METHODS: The surface of Ce-TZP-Al2O3 test specimens was alumina airborne-particle abraded (Group APA) and then treated with 10-methacryloyloxydecyl dihydrogen phosphate (MDP) (Group MDP) and 2 silica coating methods: the flame spraying method (Group SLP) and the tribochemical treatment (110 µm: Group TRB-P, 30 µm: Group TRB-S). TRB-P and TBR-S were further treated by MDP (Group CBT-P and CBT-S). Autopolymerizing acrylic resin was bonded to the specimens, and the shear bond strength was tested after thermocycling (5 °C and 60 °C, 10 000 cycles). The area of the resin remaining on the fractured surfaces was also measured. To evaluate the effect of the surface treatment condition on shear bond strength and the resin remaining, 1-way analysis of variance (ANOVA) was conducted, followed by the Tukey multiple comparison post hoc test. Additionally, the effect of thermocycling on the specimens was evaluated by the Student t test. RESULTS: After placement in deionized water for 24 hours, the shear bond strengths of Group MDP and 2 types of combination treatment (Groups CBT-P and CBT-S) were significantly higher than those of Groups SLP, TRB-P, and TRB-S (P<.05). Moreover, the fractured surface of all the treatment conditions except Group APA showed cohesive failure. The shear bond strength as a result of all treatment conditions decreased significantly after thermocycling (P<.05). Group CBT-S showed the highest shear bond strength; however, no significant differences were found between Groups CBT-S and MDP (P=.908). In particular, the area of resin remaining on the fractured surfaces of Group CBT-S was 100% (cohesive failure). CONCLUSIONS: The combined surface treatment of alumina airborne-particle abrasion and tribochemical treatment, along with primer treatment using silane coupling and an MDP monomer, improved the adhesion strength and adhesion durability between base resins and Ce-TZP-Al2O3.

A nanogel-based trivalent PspA nasal vaccine protects macaques from intratracheal challenge with pneumococci.

Current polysaccharide-based pneumococcal vaccines are effective but not compatible with all serotypes of Streptococcus pneumoniae. We previously developed an adjuvant-free cationic nanogel nasal vaccine containing pneumococcal surface protein A (PspA), which is expressed on the surfaces of all pneumococcal serotypes. Here, to address the sequence diversity of PspA proteins, we formulated a cationic nanogel-based trivalent pneumococcal nasal vaccine and demonstrated the vaccine's immunogenicity and protective efficacy in macaques by using a newly developed nasal spray device applicable to humans. Nasal vaccination of macaques with cationic cholesteryl pullulan nanogel (cCHP)-trivalent PspA vaccine effectively induced PspA-specific IgGs that bound to pneumococcal surfaces and triggered complement C3 deposition. The immunized macaques were protected from pneumococcal intratracheal challenge through both inhibition of lung inflammation and a dramatic reduction in the numbers of bacteria in the lungs. These results demonstrated that the cCHP-trivalent PspA vaccine is an effective candidate vaccine against pneumococcal infections.

Klotho supplementation attenuates blood pressure and albuminuria in murine model of IgA nephropathy.

BACKGROUND: Klotho interacts with various membrane proteins, such as transforming growth factor-ß (TGFß) and insulin-like growth factor (IGF) receptors. The renal expression of klotho is diminished in chronic kidney disease. METHOD: In this study, we assessed the effects of klotho supplementation on a murine model of IgA nephropathy. Twenty-four-week-old hyper serum IgA (HIGA) mice were subcutaneously injected daily with recombinant human klotho protein (20 µg/kg per day) or the vehicle. After 2 months, the mice were killed using an anesthesia overdose and their kidneys were harvested for analysis. RESULTS: Supplementation of exogenous klotho protein reduced SBP, albuminuria, 8-epi-prostaglandin F2α excretion, glomerular filtration rate, renal angiotensin II concentration, and angiotensinogen expression in HIGA mice. Additionally, it enhanced renal expression of superoxide dismutase (SOD) and renal klotho itself. The findings using laser-manipulated microdissection demonstrated that klotho supplementation reduced the glomerular expression of TGFß, fibronectin, and IGF, and increased the glomerular expression of connexin (Cx) 40. CONCLUSION: These results indicate that klotho supplementation reduces blood pressure by suppressing the renin--angiotensin system in HIGA mice. Klotho inhibits IGF signaling to preserve glomerular Cx40 levels, ameliorating albuminuria in HIGA mice. Klotho protein supplementation attenuates mesangial expansion by inhibiting TGFß signaling in HIGA mice.

High-resolution mechanical mapping of the adhesive-dentin interface: The effect of co-monomers in 10-methacryloyloxydecyl dihydrogen phosphate.

The presence of 10-methacryloyloxydecyl dihydrogen phosphate (MDP) at the adhesive-dentin interface enables ionic binding to calcium salts, which results in rigid nano-layering within the submicron scale resin-dentin interdiffusion zone. MDP has been used with additional co-monomers, such as hydroxyethyl methacrylate (HEMA) and/or 4-methacryloyloxyethyl-trimellitic acid (4-MET), mainly to enhance the chemical bonding properties. However, the use of co-monomers may compromise the rigidity of the adhesive-dentin interface. In this study, we use high-resolution mechanical mapping across the interface to discern the in situ mechanical properties of each target region at the nanoscale. Visualization by modulus mapping demonstrated that HEMA increases the diffusion properties of MDP into dentin structures. However, the rigidity of the adhesive-dentin interface indicated by the storage modulus was markedly lower in MDP containing HEMA than in MDP containing 4-MET. Dynamic indentation testing revealed that the bonding layer was more deformable in the presence of HEMA. Moreover, the presence of MDP in the bonding layer might also increase the deformability because the polymerization linearity allows a large degree of viscoelasticity. These factors also diminish the rigidity of the adhesive-dentin interface. Within the limitations of this study, our findings demonstrated that 4-MET is a better co-monomer than HEMA in MDP-based dental adhesives. Modulus mapping and nanoindentation are introduced as new tests for the adhesive-dentin interface to address queries about the effectiveness of dental adhesives.

Characterization and Function of Tumor Necrosis Factor and Interleukin-6-Induced Osteoclasts in Rheumatoid Arthritis.

OBJECTIVE: We have previously reported that stimulation of mouse bone marrow-derived macrophages with tumor necrosis factor (TNF) and interleukin-6 (IL-6) induces differentiation of osteoclast-like cells. We undertook this study to clarify the characterization and function of human TNF and IL-6-induced osteoclasts using peripheral blood collected from patients with rheumatoid arthritis (RA) and healthy donors. METHODS: Peripheral blood monocytes were cultured with a combination of TNF and IL-6, TNF alone, IL-6 alone, or with RANKL, and their bone resorption ability was evaluated. Expression levels of NFATc1, proinflammatory cytokines, and matrix metalloproteinase 3 were analyzed. The effects of NFAT inhibitor and JAK inhibitor were examined. Furthermore, the relationship between the number of TNF and IL-6-induced osteoclasts or RANKL-induced osteoclasts differentiated from peripheral blood mononuclear cells (PBMCs) in patients with RA and the modified total Sharp score (mTSS) or whole-body bone mineral density (BMD) was examined. RESULTS: Peripheral blood monocytes stimulated with a TNF and IL-6-induced osteoclasts were shown to demonstrate the ability to absorb bone matrix. Cell differentiation was not inhibited by the addition of osteoprotegerin. Stimulation with a combination of TNF and IL-6 promoted NFATc1 expression, whereas the NFAT and JAK inhibitors prevented TNF and IL-6-induced osteoclast formation. Expression levels of IL1ß, TNF, IL12p40, and MMP3 were significantly increased in TNF and IL-6-induced osteoclasts, but not in RANKL-induced osteoclasts. The number of TNF and IL-6-induced osteoclasts differentiated from PBMCs in patients with RA positively correlated with the mTSS, whereas RANKL-induced osteoclast numbers negatively correlated with the whole-body BMD of the same patients. CONCLUSION: Our results demonstrate that TNF and IL-6-induced osteoclasts may contribute to the pathology of inflammatory arthritis associated with joint destruction, such as RA.

Effects of Statin Plus Ezetimibe on Coronary Plaques in Acute Coronary Syndrome Patients with Diabetes Mellitus: Sub-Analysis of PRECISE-IVUS Trial.

AIM: Coronary plaque regression is weak in acute coronary syndrome (ACS) patients with diabetes mellitus (DM). We evaluated whether dual lipid-lowering therapy (DLLT) with ezetimibe and atorvastatin attenuates coronary plaques in ACS patients with DM. METHODS: The prospective, randomized controlled, multicenter PRECISE-IVUS (Plaque Regression with Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound) trial assigned 246 patients undergoing percutaneous coronary intervention to DLLT or atorvastatin monotherapy and evaluated IVUS-derived changes in percent atheroma volume (ΔPAV), at baseline and 9-12-month follow-up, in 126 ACS cases, including 25 DM patients. The atorvastatin dose was up-titrated to achieve low-density lipoprotein cholesterol (LDL-C) ＜70 mg/dL. RESULTS: In DM patients, the monotherapy group (n=13) and the DLLT group (n=12) showed a similar prevalence of coronary risks and baseline lipid profiles. During the study, the change in LDL-C level was similar between DM and non-DM patients. Compared with non-DM patients, DM patients showed weaker regression of ΔPAV by DLLT than those who underwent monotherapy (DM: -2.77±3.47% vs. -0.77±2.51%, P=0.11; non-DM: -2.01±3.36% vs. -0.08±2.66%, P=0.008). The change in LDL-C level was not correlated with ΔPAV in non-DM patients, but there was significant correlation between the change in LDL-C level and ΔPAV in DM patients (r=0.52, P=0.008). CONCLUSIONS: ACS patients with DM showed weaker coronary plaque regression than their counterparts. A significant correlation between the change in LDL-C level and ΔPAV in DM patients suggested that more intensive lipid-lowering therapy is required in ACS patients with DM.

Isotope Dilution-Total Evaporation-Thermal Ionization Mass Spectrometric Direct Determination of Radioactive Strontium-90 in Microdrop Samples.

Thermal ionization mass spectrometry (TIMS) was used to directly quantify an ultratrace of radioactive 90Sr in microliter droplet samples. No chemical separation was required in removing isobaric interferences on M = 90 such as 90Zr and organic molecules in the mass spectrum because the difference in evaporation and ionization (emission) temperature among organic molecules, Zr and Sr, allows us to control the emission manner and significantly suppress the isobaric interferences. Direct quantification was achieved by improving the intercalibration of Faraday cups and ion counting in an isotope dilution (ID) method. Furthermore, the use of a total evaporation method (TE) enhanced the detection efficiency by the complete collection of the 90Sr ion beam from the samples and minimized the complexity of the fractionation effect in the isotope ratio calculation. In this study, 1 fg of 90Sr (equal to activity of 5 millibecquerel (mBq)) in a very low-volume sample with 108 times greater isobaric interference from 90Zr was successfully measured using the proposed ID-TE-TIMS method. The limit of detection was 0.029 fg (equal to 0.15 mBq) without any preconcentration. To demonstrate the wide usability of this method, low-volume samples of tears, eyelashes, saliva, environmental standards, and water samples (i.e., seawater and ground water) were analyzed within 1 h. The relationship of the measured values between this ID-TE-TIMS method and a radiometric analysis was shown to have good linearity.

Transparent dentin region in the tooth root.

Transparent dentin in the tooth root forms during the aging process. The transparent dentin is weaker than normal opaque dentin, which may explain the occurrence of root dentin fractures in aged individuals. Tooth fractures are caused by the brittleness of the transparent dentin. Clinical procedures in aged persons require modification to accommodate the reduced strength of the dentin tissue.

3D imaging of proximal caries in posterior teeth using optical coherence tomography.

Optical coherence tomography (OCT) can create cross-sectional images of tooth without X-ray exposure. This study aimed to investigate the diagnostic accuracy of 3D imaging of OCT for proximal caries in posterior teeth. Thirty-six human molar teeth with 51 proximal surfaces visibly 6 intact, 16 slightly demineralized, and 29 distinct carious changes were mounted to take digital radiographs and 3D OCT images. The sensitivity, specificity and area under the receiver operating characteristic curve (AUC) for the diagnosis of enamel caries and dentin caries were calculated to quantify the diagnostic ability of 3D OCT in comparison with digital radiography. Diagnostic accuracy was evaluated by the agreement with histology using weighted Kappa. OCT showed significantly higher sensitivity, AUC and Kappa values than radiography. OCT can be a safer option for the diagnosis of proximal caries in posterior teeth that can be applied to the patients without X-ray exposure.

Antiferromagnetism in perfectly ordered L10-MnAl with stoichiometric composition and its mechanism.

Manganese (Mn)-based strong magnets have long been a challenge because their 3d half-filled nature, owing to the close proximity of Mn atoms, results in antiferromagnetic ordering. Among various Mn magnetic materials, L10-MnAl (τ-phase) has received much attention since it shows ferromagnetism at a high Curie temperature despite the very short Mn-Mn distance. However, because of the difficult synthesis of the stoichiometric and perfectly ordered τ-phase, its intrinsic magnetic properties and mechanism are unclear. Here, we show the first observation of antiferromagnetism, having sixfold magnetic superstructure along the c-axis, in stoichiometric and chemically ordered τ-phase. Moreover, we found that super-exchange interaction between Mn atoms via p-electrons of Al atoms causes antiferromagnetism in τ-phase. The ferromagnetism in the conventional Mn-rich τ-phase results from the suppression of the super-exchange interaction due to the substitution the excess Mn atoms for the Al atoms. The current study of Mn-based magnetic materials mainly focuses on the lattice constant engineering based on the simple Beth-Slater picture of direct exchange. These findings present effective ways to obtain high magnetization without antiferromagnetic ordering.