The N-terminal methionine of cellular proteins as a degradation signal.

The Arg/N-end rule pathway targets for degradation proteins that bear specific unacetylated N-terminal residues while the Ac/N-end rule pathway targets proteins through their N(α)-terminally acetylated (Nt-acetylated) residues. Here, we show that Ubr1, the ubiquitin ligase of the Arg/N-end rule pathway, recognizes unacetylated N-terminal methionine if it is followed by a hydrophobic residue. This capability of Ubr1 expands the range of substrates that can be targeted for degradation by the Arg/N-end rule pathway because virtually all nascent cellular proteins bear N-terminal methionine. We identified Msn4, Sry1, Arl3, and Pre5 as examples of normal or misfolded proteins that can be destroyed through the recognition of their unacetylated N-terminal methionine. Inasmuch as proteins bearing the Nt-acetylated N-terminal methionine residue are substrates of the Ac/N-end rule pathway, the resulting complementarity of the Arg/N-end rule and Ac/N-end rule pathways enables the elimination of protein substrates regardless of acetylation state of N-terminal methionine in these substrates.

Association Between Multiple Heavy Metal Exposures and Cholesterol Levels in Residents Living Near a Smelter Plant in Korea.

BACKGROUND: Considering the interactions between heavy metals, a comprehensive evaluation of the effects of exposure to various types of co-interacting heavy metals on health is required. This study assessed the association between dyslipidemia markers and blood mercury, lead, cadmium, iron, zinc, and nickel levels in residents of an abandoned refinery plant. METHODS: A total of 972 individuals (exposed group: 567, control group: 405) living near the Janghang refinery plant in the Republic of Korea were included. Blood mercury, lead, cadmium, iron, zinc, nickel, cholesterol, and triglyceride levels were measured. The combined effect of the six heavy metals on dyslipidemia markers was evaluated using a Bayesian kernel machine regression (BKMR) model and compared with the results of a linear regression analysis. The BKMR model results were compared using a stratified analysis of the exposed and control groups. RESULTS: In the BKMR model, the combined effect of the six heavy metals was significantly associated with total cholesterol (TC) levels both below the 45th percentile and above the 55th percentile in the total population. The combined effect range between the 25th and 75th percentiles of the six metals on TC levels was larger in the exposed group than that in the total population. In the control group, the combined effects of the changes in concentration of the six heavy metals on the TC concentration were not statistically significant. CONCLUSION: These results suggest that the cholesterol levels of residents around the Janghang refinery plant may be elevated owing to exposure to multiple heavy metals.

Can medication-related osteonecrosis of the jaw be attributed to specific microorganisms through oral microbiota analyses? A preliminary study.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) can cause significant pain and loss of aesthetics and function if not treated properly. However, diagnosis still relies on detailed intraoral examinations and imaging. Prognosis varies even among patients with similar stages or conditions of MRONJ, emphasizing the need for a deeper understanding of its complex mechanisms. Thus, this study aimed to identify the oral microbiota of patients with MRONJ. METHODS: This single-center prospective cohort study included patients with confirmed MRONJ who visited the Department of Oral and Maxillofacial Surgery at Yonsei University Dental Hospital between 2021 and 2022. Oral swab samples were collected from the affected and unaffected sides of each patient. The composition and enumeration of the microbial communities were analyzed, and the diversity was compared to verify ecological changes in the groups using a next-generation sequencing-based 16S metagenomic analysis. A statistical analysis was performed using Wilcoxon signed-rank test with SPSS version 22, and values of P less than 0.05 were considered statistically significant. RESULTS: The final study sample included 12 patients. The mean age was 82.67 ± 5.73 (range, 72-90) years. Changes in microbial composition were observed at different taxonomic levels (phylum, genus, and species). The identified microorganisms were commonly associated with periodontitis, gingival disease, and endodontic infection, suggesting a multifactorial etiology of MRONJ. CONCLUSIONS: Although this study is based on a small number of cases, it shows that MRONJ is not caused by a specific microorganism but can rather be caused by a variety of factors. By addressing these findings in large-scale studies, the significance of oral microbiome in pathogenesis can be further elucidated and can facilitate the development of effective therapeutic interventions for patients with MRONJ.

New approaches to moderate CRISPR-Cas9 activity: Addressing issues of cellular uptake and endosomal escape.

CRISPR-Cas9 is rapidly entering molecular biology and biomedicine as a promising gene-editing tool. A unique feature of CRISPR-Cas9 is a single-guide RNA directing a Cas9 nuclease toward its genomic target. Herein, we highlight new approaches for improving cellular uptake and endosomal escape of CRISPR-Cas9. As opposed to other recently published works, this review is focused on non-viral carriers as a means to facilitate the cellular uptake of CRISPR-Cas9 through endocytosis. The majority of non-viral carriers, such as gold nanoparticles, polymer nanoparticles, lipid nanoparticles, and nanoscale zeolitic imidazole frameworks, is developed with a focus toward optimizing the endosomal escape of CRISPR-Cas9 by taking advantage of the acidic environment in the late endosomes. Among the most broadly used methods for in vitro and ex vivo ribonucleotide protein transfection are electroporation and microinjection. Thus, other delivery formats are warranted for in vivo delivery of CRISPR-Cas9. Herein, we specifically revise the use of peptide and nanoparticle-based systems as platforms for CRISPR-Cas9 delivery in vivo. Finally, we highlight future perspectives of the CRISPR-Cas9 gene-editing tool and the prospects of using non-viral vectors to improve its bioavailability and therapeutic potential.

Small-molecule inhibitors of histone deacetylase improve CRISPR-based adenine base editing.

CRISPR-based base editors (BEs) are widely used to induce nucleotide substitutions in living cells and organisms without causing the damaging DNA double-strand breaks and DNA donor templates. Cytosine BEs that induce C:G to T:A conversion and adenine BEs that induce A:T to G:C conversion have been developed. Various attempts have been made to increase the efficiency of both BEs; however, their activities need to be improved for further applications. Here, we describe a fluorescent reporter-based drug screening platform to identify novel chemicals with the goal of improving adenine base editing efficiency. The reporter system revealed that histone deacetylase inhibitors, particularly romidepsin, enhanced base editing efficiencies by up to 4.9-fold by increasing the expression levels of proteins and target accessibility. The results support the use of romidepsin as a viable option to improve base editing efficiency in biomedical research and therapeutic genome engineering.

Exposure to Hazardous Substances and Their Health Effects Among Residents Living Near Three Industrial Waste Incinerators in Korea.

BACKGROUND: This study aimed to evaluate exposure to various hazardous substances emitted by incineration facilities and their likely effect on the health for residents of Bugi-myeon, Cheongju, Korea, which has three incineration facilities. METHODS: Heavy metals, polycyclic aromatic hydrocarbons (PAHs), and dioxin concentrations in the air and soil of exposed and control areas were measured. Moreover, the exposure levels to harmful substances and its effects on health were investigated in 1,124 exposed and 232 control adults. RESULTS: PAHs and dioxin concentrations in the air in the exposed area were significantly higher than in the control area. Urinary cadmium and PAHs metabolite concentrations were significantly higher in the exposed group than in the control group. The exposure group also had a higher prevalence of depression and self-reported allergic symptoms than the control group. CONCLUSION: The possibility of residents in Bugi-myeon being exposed to hazardous substances at incineration facilities cannot be ruled out. To prevent them from further exposure to hazardous substances, it is necessary to prohibit the expansion of additional incineration facilities in this area and to implement continuous monitoring projects for residents.

Effects of Environmental Cadmium Exposure on the Liver in Korean Adults: Cross-Sectional and Longitudinal Studies.

Cadmium (Cd) is a ubiquitous environmental pollutant with an exceptionally long biological half-life. The liver is a major organ for Cd metabolism, but the toxicity of Cd is unclear. This study sought to determine whether blood Cd (BCd) level (representing recent exposure [months] to Cd) was associated with liver function in Korean adults, both cross-sectionally and longitudinally. The baseline cross-sectional study involved 2,086 adults (male: 908, female: 1,178) in 2010 - 2011, and 503 of them (male: 207, female: 296) were followed up in 2014 - 2015. BCd was measured by graphite-furnace atomic absorption spectrometry, and liver function indices (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and γ-glutamyltransferase [GGT]) were determined. Liver damage was defined as an abnormal elevation of more than one liver function index. The geometric mean of BCd (1.07 µg/L) was higher in females than in males (1.16 vs. 0.96 µg/L). Liver function indices increased significantly in a dose-dependent manner according to the BCd levels, except for ALT in males, and were higher in males than in females. BCd level was also associated with the risk of liver damage in both sexes. No significant changes in BCd were observed between baseline and follow-up. The liver function indices in 2014 - 2015 were comparable to those in 2010 - 2011 in males, while ALT and GGT were significantly increased in 2014 - 2015 compared to 2010 - 2011 in females with relatively high BCd. These findings suggest that even a low level of environmental Cd exposure, short- and long-term, may affect liver function, and females appear more susceptible than males.

Cancer risk in the residents of a town near three industrial waste incinerators in Korea: a retrospective cohort study.

BACKGROUND: Three industrial waste incinerators (IWIs) were built in 1999, 2001, and 2010, within a 3 km radius of a town with a population of around 5000 in Korea. This study evaluated whether residents near these three IWIs had increased cancer incidence than those from other areas in Korea using regional health data. METHODS: Standardized incidence ratios (SIR) were calculated using the frequency of cancer cases in the National Cancer Registry of the exposed area (Buki-myeon), Chungcheongbuk-do (Chungbuk, state including Buki-myeon), and whole Korea from 1999 to 2017. A retrospective cohort was created using National Health Insurance System data from 2002 to 2018. The exposed group was defined as those having a residential history in the exposed area. The control group was defined as those having a residential history in nearby towns or counties in Chungbuk, excluding counties having living and cultural areas in other provinces and cities. Hazard ratio (HR) and 95% confidence intervals (CI) were estimated using the Cox proportional hazard model adjusted for age, level of health insurance fee, and smoking history. RESULTS: In the ecological study using National Cancer Registry data, the risk of all cancers, all cancers excluding thyroid, esophageal, stomach, and lung cancers in the exposed area were 1.13 (95% CI 1.03-1.24), 1.15 (95% CI 1.04-1.26), 1.91 (95% CI 1.13-2.89), 1.39 (95% CI 1.14-1.66), and 1.29 (95% CI 1.03-1.57) times higher than in whole Korea among exposed males, respectively. In the retrospective cohort, 4300 males (26,821 person-years) and 3796 females (24,746 person-years) in exposed group, 150,964 males (1,212,010 person-years) and 134,535 females (1,104,025 person-years) in control group were analyzed. After adjusting for several confounding factors, the risks for gallbladder cancer among males and kidney cancer among females were 2.65 (95% CI 1.38-5.06) and 2.82 (95% CI 1.13-7.03) times higher in the exposed group versus the control group, respectively. CONCLUSIONS: Cancer risk was higher in Koreans having residential history living near IWIs compared to the other areas. Further study warrants nationwide effects and longer follow-up of WIs for cancers in Korea.

Exposure Levels and Contributing Factors of Various Arsenic Species and Their Health Effects on Korean Adults.

Arsenic is a human carcinogen. Data on urinary arsenic species analyses of Koreans are limited. This study evaluated the arsenic exposure level, contributing factors, and health effects in Korean adults. Dietary intake information and urine samples were obtained from 2044 participants. Arsenic exposure was assessed based on urinary concentrations of arsenic species, such as inorganic arsenic, As(III) and As(V), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and arsenobetaine (AsB), using high-performance liquid chromatography with inductively coupled plasma mass spectrometry, followed by determination of biomarkers, malondialdehyde and c-peptide. The geometric mean concentrations were 30.9 µg/L for the sum of inorganic arsenic and their metabolites, and 84.7 µg/L for the total sum of arsenic measured. Urinary concentrations of arsenic species were influenced by age, inhabitant area (inland or coastal), and seafood intake, which was positively correlated with inorganic arsenic, DMA, and AsB. Rice intake was positively correlated with inorganic arsenic and its metabolites but not with AsB. Additionally, malondialdehyde and c-peptide levels were significantly associated with urinary concentrations of various arsenic species. Seafood and rice are major sources of organic/inorganic arsenic exposure in Korean adults; however, it is necessary to evaluate whether their overconsumption could have a potentially detrimental effect on human health.

Evaluation of Commercial Corrosion Sensors for Real-Time Monitoring of Pipe Wall Thickness under Various Operational Conditions.

In this study, we investigated the performance and reliability of commercial corrosion sensors for monitoring the integrity of piping systems in various fluid environments as an alternative to ultrasonic transducers. To this end, we investigated pipes' wall-thinning using commercial electrical resistance (ER), linear polarization resistance (LPR), and ultrasonic transducer (UT) sensors under various operating environments. A pilot-scale closed-loop test bed was built to simulate a real pipeline flow situation, from which the sensor data were collected and analyzed. Experimental results indicate that, in the case of the LPR sensor, it is challenging to accurately measure the corrosion rate when a specific measure exceeds the threshold in a severe corrosion environment. In contrast, the ER sensor could measure metal loss under all conditions and reflect the corresponding characteristics. The metal loss (about 0.25 mm) of the real pipe after the experiment was confirmed to be equal to the metal loss (0.254 mm) measured by the sensor. Furthermore, the regression analysis revealed a high correlation between the results obtained from the ER and UT sensors. Thus, evaluating the remaining thickness of the piping system using the commercial ER sensor is deemed to be effective and reliable.

A novel needle-free microjet drug injector using Er:YAG LASER: A completely new concept of transdermal drug delivery system.

The skin barrier effectively inhibits the penetration of substances; therefore, drug delivery, especially the delivery of drugs that are hydrophilic, through the skin, is challenging. Objectives: Physicians in the esthetic field now use the transdermal drug delivery system to attempt to deliver esthetic materials, such as hyaluronic acid and poly-DL-lactic acid into the skin. Conventionally, esthetic physicians manually injected these materials using needle syringes into the dermis layer. However, the injection is often irregular, imprecise, slow, and painful. Injector devices have been developed to overcome these limitations. A total of five Korean cadavers (that of three men and two women with a mean age of 69.2 years; range, 60-73 years) underwent laser injection. We used a device called Er:YAG LASER to create the pressure needed for microjet delivery to the skin of the cadaver. Discussion: In this study, the first LASER pressure-based, needle-free microjet injector was used to deliver drugs effectively into the dermis of a cadaver. This study showed that a novel needle-free microjet injector using Er:YAG LASER can introduce beneficial, liquid, esthetic drugs into the papillary dermal layer (depth of 300um) with minimal epidermal damage.

Changes in Isoflavone Profile from Soybean Seeds during Cheonggukjang Fermentation Based on High-Resolution UPLC-DAD-QToF/MS: New Succinylated and Phosphorylated Conjugates.

In this study, thirty-eight isoflavone derivatives were comprehensively identified and quantified from the raw, steamed and fermented seeds of four selected soybean cultivars based on UPLC-DAD-QToF/MS results with reference to the previously reported LC-MS library and flavonoid database, and summarized by acylated group including glucosides (Glu), malonyl-glucosides (Mal-Glu), acetyl-glucosides (Ac-Glu), succinyl-glucosides (Suc-Glu) and phosphorylated conjugates (Phos) in addition to aglycones. Among them, Suc-Glu and Phos derivatives were newly generated due to fermentation by B. subtilis AFY-2 (cheonggukjang). In particular, Phos were characterized for the first time in fermented soy products using Bacillus species. From a proposed roadmap on isoflavone-based biotransformation, predominant Mal-Glu (77.5-84.2%, raw) decreased rapidly by decarboxylation and deesterification into Ac-Glu and Glu (3.5-8.1% and 50.0-72.2%) during steaming, respectively. As fermentation continued, the increased Glu were mainly succinylated and phosphorylated as well as gradually hydrolyzed into their corresponding aglycones. Thus, Suc-Glu and Phos (17.3-22.4% and 1.5-5.4%, 36 h) determined depending on cultivar type and incubation time, and can be considered as important biomarkers generated during cheonggukjang fermentation. Additionally, the changes of isoflavone profile can be used as a fundamental report in applied microbial science as well as bioavailability research from fermented soy foods.

A SLC35C2 Transporter-Targeting Fluorescent Probe for the Selective Detection of B Lymphocytes Identified by SLC-CRISPRi and Unbiased Fluorescence Library Screening.

T and B lymphocytes are two major adaptive immune cells in the human defense system. To real-time monitor their diverse functions, a live-cell-selective probe for only one cell type is need to investigate the complex interaction of the immune cells. Herein, a small-molecule probe CDyB for live B cells is developed by an unbiased fluorescence library screening. The cell selectivity was confirmed by multiparametric single-cell analysis using CyTOF. Through a systematic SLC-CRISPRi library screening, the molecular target of CDyB was identified as SLC35C2 transporter based on a gating-oriented live-cell distinction (GOLD) mechanism. The gene expression analysis and knock-out experiments validated that the SLC35C2 transporter was the target for CDyB distinction. Interestingly, when CDyB was applied to study B cell development, the CDyB fluorescence and SLC35C2 expression were positively correlated with the B cell maturation process, and not involved in the T cell development.

Arrayed CRISPR screen with image-based assay reliably uncovers host genes required for coxsackievirus infection.

Pooled CRISPR screens based on lentiviral systems have been widely applied to identify the effect of gene knockout on cellular phenotype. Although many screens were successful, they also have the limitation that genes conferring mild phenotypes or those essential for growth can be overlooked, as every genetic perturbation is incorporated in the same population. Arrayed screens, on the other hand, incorporate a single genetic perturbation in each well and could overcome these limitations. However, arrayed screens based on siRNA-mediated knockdown were recently criticized for low reproducibility caused by incomplete inhibition of gene expression. To overcome these limitations, we developed a novel arrayed CRISPR screen based on a plasmid library expressing a single guide RNA (sgRNA) and disrupted 1514 genes, encoding kinases, proteins related to endocytosis, and Golgi-localized proteins, individually using 4542 sgRNAs (three sgRNAs per gene). This screen revealed host factors required for infection by coxsackievirus B3 (CVB3) from Picornaviridae, which includes human pathogens causing diverse diseases. Many host factors that had been overlooked in a conventional pooled screen were identified for CVB3 infection, including entry-related factors, translational initiation factors, and several replication factors with different functions, demonstrating the advantage of the arrayed screen. This screen was quite reliable and reproducible, as most genes identified in the primary screen were confirmed in secondary screens. Moreover, ACBD3, whose phenotype was not affected by siRNA-mediated knockdown, was reliably identified. We propose that arrayed CRISPR screens based on sgRNA plasmid libraries are powerful tools for arrayed genetic screening and applicable to larger-scale screens.

Development of a SARS-CoV-2-derived receptor-binding domain-based ACE2 biosensor.

The global outbreak of coronavirus disease and rapid spread of the causative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent a significant threat to human health. A key mechanism of human SARS-CoV-2 infection is initiated by the combination of human angiotensin-converting enzyme 2 (hACE2) and the receptor-binding domain (RBD) of the SARS-CoV-2-derived spike glycoprotein. Despite the importance of these protein interactions, there are still insufficient detection methods to observe their activity at the cellular level. Herein, we developed a novel fluorescence resonance energy transfer (FRET)-based hACE2 biosensor to monitor the interaction between hACE2 and SARS-CoV-2 RBD. This biosensor facilitated the visualization of hACE2-RBD activity with high spatiotemporal resolutions at the single-cell level. Further studies revealed that the FRET-based hACE2 biosensors were sensitive to both exogenous and endogenous hACE2 expression, suggesting that they might be safely applied to the early stage of SARS-CoV-2 infection without direct virus use. Therefore, our novel biosensor could potentially help develop drugs that target SARS-CoV-2 by inhibiting hACE2-RBD interaction.

Effects of Exposure to Lead and Cadmium on Health of Inhabitants of Abandoned Metal Mine Area in Korea.

People living near abandoned mines are at increased risk of exposure to toxic metals. We surveyed 4500 inhabitants with the mean age of 68.5 years old (male: 1768, female: 2732) living near 104 abandoned metal mines from 2013 to 2017 (the 2nd phase health survey in Korea). We conducted personal interviews, blood and urine sampling, and analyzed the concentrations of lead (Pb) and cadmium (Cd) in whole blood and Cd in urine using a graphite furnace atomic absorption spectrometer. The geometric means of blood Pb, blood Cd, and urine Cd were 2.27 µg/dL, 1.42 µg/L, and 1.66 µg/g creatinine, respectively. The level of metal exposure was lower than that reported from the first phase health survey in Korea (2008‒2011) but was higher than in the general population of Korea. Blood Pb was higher in males while blood Cd and urine Cd were significantly higher in females. Blood Pb was highest in the 40‒59 age group, while blood and urine Cd levels continuously increased until age 80 or older. The Cd levels in blood and urine were affected by consumption of locally produced rice and duration of residence near abandoned mines. Furthermore, negative correlations were observed between blood Pb and blood and urine Cd levels. Additionally, 252 of the 4500 subjects exceeded the thresholds of blood Cd or urine Cd levels. Together, these findings suggest that Cd has more sustainable and adverse health effects on the abandoned mine inhabitants, who are mostly aged. Therefore, continuous biomonitoring and risk assessment to environmental health risks are necessary for environmental pollution control and health promotion.

Characterization of Saponins from Various Parts of Platycodon grandiflorum Using UPLC-QToF/MS.

Platycodon grandiflorum (PG) is known as a high-potential material in terms of its biological activity. The objective of this report is to provide chromatographic and mass fragment ion data of 38 simultaneously identified saponins, including novel compounds, by analyzing them through ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QToF/MS). In so doing, we investigated their diverse conditions, including morphological parts (stems, roots, buds, and leaves), peeling (or not), and blanching of PG. The total contents of individual saponins indicated an order of roots (containing peel, 1674.60 mg/100 g, dry weight) > buds (1364.05) > roots (without peel, 1058.83) ≈ blanched roots (without peel, 945.17) ≈ stems (993.71) ≈ leaves (881.16). When considering three types of aglycone, the platycodigenin group (55.04 ~ 68.34%) accounted for the largest proportion of the total content, whereas the platycogenic acid A group accounted for 17.83 ~ 22.61%, and the polygalacic acid group represented 12.06 ~ 22.35%. As they are classified as major compounds, novel saponins might be utilized for their role in healthy food for human consumption. Additionally, during blanching, the core temperature of PG was satisfied with the optimal condition, thus activating the enzymes related to biotransformation. Furthermore, through the use of this comprehensive data, additional studies related to buds, as well as roots or the characterization of individual saponins, can be conducted in a rapid and achievable manner.

Copper-zinc imbalance induces kidney tubule damage and oxidative stress in a population exposed to chronic environmental cadmium.

PURPOSE: This cross-sectional study aimed to assess the effect of environmental cadmium (Cd) exposure and essential metal imbalance on renal tubular damage and oxidative stress in 979 adults living in a Cd-polluted area near an abandoned copper (Cu) refinery. METHODS: We analyzed urinary Cd concentrations, renal tubular damage and oxidative stress markers, such as beta-2 microglobulin (ß2-MG) and N-acetyl-ß-D-glucosaminidase (NAG) activity and urine malondialdehyde (MDA) levels. The serum copper-to-zinc ratio (CZR) was used as an essential metal imbalance indicator. We divided the subjects into two Cd exposure groups based on the reference level of urinary Cd for renal dysfunction (2 µg/g creatinine). RESULTS: The geometric mean concentration of urinary Cd in all subjects was 2.25 µg/g creatinine. In both low and high Cd exposure groups, urinary Cd levels were positively correlated with urinary NAG activity, but not with serum CZR. After multivariate adjustment, serum CZR was strongly associated with urinary ß2-MG levels in the low Cd exposure group (ß = 1.360, P = 0.019) and was significantly associated with urinary MDA levels, regardless of Cd exposure level. In addition, the risk of renal tubular damage was significantly associated with urinary Cd level, particularly in the lowest or highest CZR tertile groups. CONCLUSIONS: Essential metal imbalance may be a determinant of oxidative stress and renal tubular damage in a chronically Cd-exposed population, and proper zinc supplementation will be effective in preventing adverse health effects due to Cd exposure.

Effect of PTH and corticotomy on implant movement under mechanical force.

BACKGROUND: Osseointegrated implants are considered as clinically non-movable. Parathyroid hormone (PTH) is known to play a significant role in the regulation of bone remodeling and in intermittent, low doses, result in osteoanabolic effects. This study aimed to investigate the effects of PTH and corticotomy, both under traction force, on osseointegrated implants. METHODS: Four implants-two in each hemimandible-were placed in each of the three study mongrels. Each mongrels were designated as control, normal dose PTH (PTH-1), and high dose PTH (PTH-2) groups, with each groups further subdivided into non-surgery implant and surgery implant. After osseointegration, mechanical force with NiTi closed coil springs (500 g) was applied around each implants. Corticotomy was performed around one of four implants in each mongrels. Parathyroid hormone was administered locally on a weekly basis for 20 weeks. Clinical movement of the implants were evaluated with the superimposed 3D- scanned data, bone- microarchitectural and histologic examinations. RESULTS: Superimposition analysis showed continuous movement of the non-surgery implant of PTH-1 group. Movement was further justified with lowest bone implant contact (adjusted BIC; 44.77%) in histomorphometric analysis. Upregulation of bone remodeling around the implant was observed in the normal dose PTH group. In the surgery implants, the remarkably higher adjusted BIC compared to the non-surgery implants indicated increased bone formation around the implant surface. CONCLUSION: The results indicate that the catabolic and anabolic balance of osseointegrated implants in terms of bone remodeling can be shifted via various interventions including pharmacological, surgical and mechanical force. CLINICAL RELEVANCE: Upregulated bone remodeling by PTH and corticotomy under continuous mechanical force showed the possible implications for the movement of osseointegrated dental implant.

Ultrathin-Polyaniline-Coated Pt-Ni Alloy Nanooctahedra for the Electrochemical Methanol Oxidation Reaction.

Controlling the morphology and composition of nanocatalysts constructed from metals and conductive polymers has attracted attention owing to their great potential for the development of high-efficiency catalysts for various catalytic applications. Herein, a facile synthetic approach for ultrathin-polyaniline-coated Pt-Ni nanooctahedra (Pt-Ni@PANI hybrids) with controllable PANI shell thicknesses is presented. Pt-Ni nanooctahedra/C catalysts enclosed by PANI shells with thicknesses from 0.6 to 2.4 nm were obtained by fine control over the amount of aniline. The various Pt-Ni@PANI hybrids exhibited electrocatalytic activity toward the methanol oxidation reaction that is highly dependent on the thickness of the PANI shell. Pt-Ni@PANI hybrids with the thinnest PANI shells (0.6 nm) showed markedly improved electrocatalytic performance for the methanol oxidation reaction compared with Pt-Ni@PANI hybrids with thicker PANI shells, Pt-Ni nanooctahedra/C, and commercial Pt/C due to synergistic benefits of ultrathin PANI shells and Pt-Ni alloy.