Classification of Angelica species found in various foods using an LC-QTOF/MS-based metabolomics approach.

In Korea, Angelica gigas is commonly known as Danggui. However, two other species on the market, Angelica acutiloba and Angelica sinensis, are also commonly called Danggui. Since the three Angelica species have different biologically active components, thus, different pharmacological activities, clear discrimination between them is needed to prevent their misuse. A. gigas is used not only as a cut or powdered product but also in processed foods, where it is mixed with other ingredients. To discriminate between the three Angelica species, reference samples were analysed as non-targeted using liquid chromatography-quadrupole time of flight/mass spectrometry (LC-QTOF/MS) and a metabolomics approach in which a discrimination model was established by partial least squares-discriminant analysis (PLS-DA). Then, the Angelica species in the processed foods were identified. First, 32 peaks were selected as marker compounds and a discrimination model was created using PLS-DA, and its validation was confirmed. Classification of the Angelica species was undertaken using the YPredPS value, and it was confirmed that all 21 foods examined contained the appropriate Angelica species indicated on the product packaging. Likewise, it was confirmed that all three Angelica species were accurately classified in the samples to which they were added.

Reproduction Factor Based Latent Epidemic Model Inference: A Data-Driven Approach Using COVID-19 Datasets.

The mathematical modeling of infectious diseases aims to evaluate the transmissibility of the on-going spread of disease and guide the government's control strategies and interventions. In this paper, we propose a novel transmissibility indicator, reproduction factor, which evaluates the number of secondary infections from a single nonisolated infectious individual. In contrast to classic reproduction numbers, the reproduction factor explicitly considers the fraction of susceptible individuals (who are not immune to disease naturally or through vaccination) and the nonisolated population to evaluate near real-time transmissibility. Thus, it can be an effective indicator when the spread of disease has progressed and control strategies have been implemented. Other merits of the proposed reproduction factor include data-driven inference based on a Markov chain, which enables the inference of latent information, such as the number of nondetected infectious individuals and the number of daily new infections. We performed an extensive simulation using the COVID-19 datasets of Germany, Italy, South Korea, and California (the U.S.) to verify our model. We further compared the results with other transmissibility measures, including reproduction numbers, and the results of state-of-the-art epidemic models. Through the results, we confirmed that the proposed reproduction factor and corresponding inference model explained the COVID-19 datasets.

SYNCRIP controls miR-137 and striatal learning in animal models of methamphetamine abstinence.

Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome. Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA-target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine (MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR, LC-MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.

Discrimination of three Angelica herbs using LC-QTOF/MS combined with multivariate analysis.

Angelica gigas, a popular medicinal herb in Korea, is locally called Danggui; this name is similarly used for Angelica acutiloba and Angelica sinensis, which are also sold in the retail market. These three herbs have differing therapeutic effects and should be used according to their prescribed purposes. In some retail markets, though, all three herbs are known by the same common name rather than a scientific name and can therefore be confused with each other. In particular, in the case of powdered products, intentional or unintentional wrong sales activity by the seller may occur. In this study, non-targeted analysis was performed using liquid chromatography quadrupole time-of-flight mass spectrometry to discriminate between the three Angelica herbs, and marker compounds were identified by principal component analysis. Principal component analysis was applied to the whole dataset with the variables being sample name, peak name (m/z with retention time), and ion intensity extracted in advance by peak finding, alignment, and filtering. All three herbs were visually and clearly differentiated in the score plot, and the marker compounds that contributed to their discrimination were found in the loading plot through principal component variable grouping (PCVG). Among the marker compounds, coumarins contributed to the classification of A. gigas, and phthalides contributed to the classification of A. sinensis. The three Angelica herbs were well discriminated from each other. Within the three Angelica species investigated, marker compounds can determine the species of even powdered or extracted samples that cannot be visually identified.

Claustral MeCP2 Regulates Methamphetamine-induced Conditioned Place Preference in Cynomolgus Monkey.

The claustrum, a brain nucleus located between the cortex and the striatum, has recently been highlighted in drug-related reward processing. Methyl CpG-binding protein-2 (MeCP2) is a transcriptional regulator that represses or activates the expression of the target gene and has been known to have an important role in the regulation of drug addiction in the dopaminergic reward system. The claustrum is an important region for regulating reward processing where most neurons receive dopamine input; additionally, in this region, MeCP2 is also abundantly expressed. Therefore, here, we hypothesized that MeCP2 would be involved in drug addiction control in the Claustrum as well and investigated how claustral MeCP2 regulates drug addiction. To better understand the function of human claustral MeCP2, we established a non-human primate model of methamphetamine (METH) - induced conditioned place preference (CPP). After a habituation of two days and conditioning of ten days, the CPP test was conducted for three days. Interestingly, we confirmed that virus-mediated overexpression of MECP2 in the claustrum showed a significant reduction of METH-induced CPP in the three consecutive days during the testing period. Moreover, they showed a decrease in visit scores (frequency for visit) for the METH-paired room compared to the control group although the scores were statistically marginal. Taken together, we suggest that the claustrum is an important brain region associated with drug addiction, in which MeCP2 may function as a mediator in regulating the response to addictive drugs.

Discovery of 4H-chromeno[2,3-d]pyrimidin-4-one derivatives as senescence inducers and their senescence-associated antiproliferative activities on cancer cells using advanced phenotypic assay.

Current research suggests therapy-induced senescence (TIS) of cancer cells characterized by distinct morphological and biochemical phenotypic changes represent a novel functional target that may enhance the effectiveness of cancer therapy. In order to identify novel small-molecule inducers of cellular senescence and determine the potential to be used for the treatment of melanoma, a new method of high-throughput screening (HTS) and high-contents screening (HCS) based on the detection of morphological changes was designed. This image-based and whole cell-based technology was applied to screen and select a novel class of antiproliferative agents on cancer cells, 4H-chromeno[2,3-d]pyrimidin-4-one derivatives, which induced senescence-like phenotypic changes in human melanoma A375 cells without serious cytotoxicity against normal cells. To evaluate structure-activity relationship (SAR) study of 4H-chromeno[2,3-d]pyrimidin-4-one scaffold starting from hit 3, a focused library containing diversely modified analogues was constructed and which led to the identification of 38, a novel compound to have remarkable anti-melanoma activity in vitro with good metabolic stability.

Determination of 12 herbal compounds for estimating the presence of Angelica Gigas Root, Cornus Fruit, Licorice Root, Pueraria Root, and Schisandra Fruit in foods by LC-MS/MS.

A wide variety of plant raw materials thought to promote health are used as herbal medicines as well as foods. However, there is no legal maximum or minimum concentration limit on any herbal compound when these plant raw materials are used in processed foods. Legally, these processed foods are regulated only for harmful substances, and there is no other guarantee of their contents. Therefore, the objective of this study was to determine the concentrations of 12 herbal compounds (nodakenin, decursin, decursinol angelate, morroniside, loganin, glycyrrhizic acid, liquiritigenin, puerarin, daidzin, schisandrin, gomisin A, gomisin N) in commonly used plant raw materials, such as "Angelica Gigas root", "Cornus Fruit", "Liquorice Root", "Pueraria Root", and "Schisandra Fruit"; and also in 45 processed foods, using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Method validation was performed successfully using the parameters of specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, matrix effect, extraction recovery, and stability. The 12 herbal compounds were determined to be present in all the foods advertised as containing each ingredient, although in very low concentrations in some cases. Three solid samples labelled as 100% pure material from one herbal species also contained herbal compounds found in others, so that intentional or unintentional adulteration was suspected.

Designing a mandibular advancement device with topology optimization for a partially edentulous patient.

STATEMENT OF PROBLEM: Patients with partial tooth loss treated with implant-supported fixed partial dentures (FPDs) have difficulty using conventional mandibular advancement devices (MADs) because of the risk of side effects. Also, which design factors affect biomechanical stability when designing MADs with better stability is unclear. PURPOSE: The purpose of this finite element (FE) analysis study was to analyze the effect of the MAD design on biomechanical behavior and to propose a new design process for improving the stability of MADs. MATERIAL AND METHODS: Each 3D model consisted of the maxillofacial bones, teeth, and implant-supported FPDs located in the left tooth loss area from the first premolar to the second molar and a MAD. Three types of custom-made MADs were considered: a complete-coverage MAD covering natural tooth-like conventional MADs, a shortened MAD excluding the coverage on the implant-supported FPD, and a newly designed MAD without anterior coverage. For the new MAD design, topology optimization was conducted to reduce the stress exerted on the teeth and to improve retention of the MAD. The new MAD design was finished by excluding the coverage of the maxillary and mandibular central incisors based on the results of the topology optimization. A mandibular posterior restorative force for a protrusion amount of 40% was used as the loading condition. The principal stress and pressure of the cancellous bone and periodontal ligaments (PDLs) were identified. RESULTS: Considering the load concentration induced by the complete-coverage MAD, bone resorption risk and root resorption risk were observed at both ends of the mandibular teeth. The shortened MAD resulted in the highest stress concentration and pressure with the worst stability. However, in the case of the complete-coverage MAD, the pressure in the PDLs was reduced to the normal range, and the risk of root resorption was reduced. CONCLUSIONS: For patients with implant-supported FPDs, MAD designs with different extents of coverage had an influence on biomechanical behavior in terms of stress distribution in cancellous bone and PDLs. A MAD design without anterior coverage provided improved stability compared with complete-coverage or shortened designs. The presented method for MAD design, which combined FE analysis and topology optimization, could be effectively applied in the design of such improved MADs.

Supersensitive Detection of the Norovirus Immunoplasmon by 3D Total Internal Reflection Scattering Defocus Microscopy with Wavelength-Dependent Transmission Grating.

Norovirus (NoV) is a major foodborne pathogen, and even low levels of virus can cause infection and gastroenteritis. We developed a supersensitive NoV sensor that detects NoV group-I capsid protein (NoVP) via three-dimensional (3D) total internal reflection scattering defocus microscopy (TIRSDM) with wavelength-dependent transmission grating (TG). The combination of evanescent wave scattering and TG significantly enhanced the detection sensitivity and selectivity of NoVP in first-order spectral images (n = +1) by minimizing spectroscopic interference and background noise. In particular, wavelength-dependent 3D defocused TG imaging (3D TG-TIRSDM) separated silver nanotag and gold nanoplate signals on a NoVP immunoplasmon chip along the x, y, and z coordinates simultaneously. Additionally, the use of wavelength-dependent TG increased the spectral resolution by 5-fold along the xy-axis and 1.4-fold along the z-axis compared to conventional 3D TIRSDM at the subdiffraction limit. The NoVP sensor exhibited a lower limit of detection of 820 yM, which is 29 000 times better than the previous potentiometer method, and a wide dynamic detection range of 820 yM to 92.45 pM (R = 0.9801). This new method could be applied to detect various pathogenic viruses during the initial stage of infection.

Comparison of Physicochemical Characteristics of Garlic Produced from South Korea and China.

Garlic is widely cultivated and frequently used as a spice in South Korea, due to its characteristic flavor. It is rich in sulfur-containing compounds (for example, allicin) and nonsulfur elements (for example, phosphorus and potassium). During the last few years, the cultivation area of garlic in South Korea has gradually decreased, one of the reasons being the increase in low-priced imported garlic from China. Several studies have reported the discrimination of foods originating from different geographical areas by analyzing their physicochemical properties using various statistical methods. In this study, the differentiation of geographical origin of garlic between South Korea (60 samples) and China (41 samples) was performed by analyzing their physicochemical properties (for example, pH, soluble solid, moisture, free sugars, mineral elements, total flavonoid, and total phenolic contents) combined with statistical methods. The significant difference between domestic garlic from South Korea and imported garlic from China was investigated in terms of pH, moisture content, total flavonoid content, and all trace minerals except for manganese and magnesium. Logistic regression analysis was performed to determine the geographical origin (South Korea or China) of garlic after selecting the appropriate independent variables. As a result, the calculated logistic regression equation from the analysis of copper, iron, phosphorus, zinc, and sucrose contents could be used to determine whether the geographical origin of garlic was South Korea or China. PRACTICAL APPLICATION: Despite being widely used in South Korea, the cultivation area of garlic in South Korea has gradually decreased over the last few years. One of the reasons is the increase in low-priced imported garlic from China. To discriminate the geographical origin of garlic between South Korea and China, analyzed physicochemical properties (that is, Cu, Fe, P, Zn, and sucrose contents) of garlic in combination with logistic regression analysis can be helpful for scientists working on food forensics. This discrimination technique can help to maintain the quality of garlic and prevent economic fraud by confirming the authenticity of garlic from South Korea.

Characterization of pork patties containing dry radish (Raphanus sativus) leaf and roots.

OBJECTIVE: This study investigated the effects of dry radish leaf and root on the quality of pork patties during refrigeration storage. METHODS: The patties were divided into the following three groups: the control containing 0% dry radish leaf root powder, RL1 containing 0.5% dry radish leaf root powder, and RL2 and RL3 containing 1% and 2% dry radish leaf root powder, respectively. Proximate composition, pH, cooking loss, microbial analysis, lipid oxidation analysis, color, texture profile analysis and sensory test were performed. RESULTS: Moisture, crude protein, and crude ash contents in RL2 and RL3 were significantly higher than those in other groups (p<0.05), whereas crude fat contents in RL2 and RL3 were significantly lower than other groups (p<0.05). Lightness was significantly lower in RL2 and RL3 than in CON (p<0.05). Cooking loss for RL2 and RL3 were significantly lower than those for the other groups (p<0.05). The pH, thiobarbituric acid levels, and total plate counts of RL2 and RL3 were significantly lower than those of CON at days 7 and 14 (p<0.05). Hardness values of RL2 and RL3 were significantly lower than those of CON, whereas chewiness values were higher than those of CON (p<0.05). In addition, the juiciness of RL2 were significantly greater (p<0.05) than those of the other groups. CONCLUSION: Dried radish leaves and roots improved the proximate composition and quality characteristics of pork patties, providing a basis to produce high-quality patties with extended expiration dates. Thus, dried radish leaves and roots are effective ingredients for health or functional foods.

Biomechanical effect of mandibular advancement device with different protrusion positions for treatment of obstructive sleep apnoea on tooth and facial bone: A finite element study.

BACKGROUND: The mandibular advancement device (MAD) is widely used for obstructive sleep apnoea (OSA) treatment, and several studies have demonstrated its effectiveness. However, no comprehensive studies have yet examined the biomechanical safety of the MAD. OBJECTIVES: The objective of this study was to analyse the biomechanical effect of different protrusion positions of a MAD on the teeth and facial bones. METHODS: The posterior restorative forces due to the stretched mandibular muscles were measured by pressure sensors attached to the experimental mandibular advancement device for mandibular protrusions of 10-70% of the maximum protrusion of the subject. A detailed three-dimensional biomechanical model of the study subject, constructed from computed tomography scans, was used in finite element analysis, with loading conditions calculated from the measured posterior restorative forces. The outcome measures were the principal stresses on the periodontal ligaments (PDL) and cancellous bone, and the pressure at the PDL surfaces. The measurements were used to analyse the risk of the tooth movement, tooth root resorption, and bone resorption. RESULTS: The lowest and highest restorative forces occurred at 40% and 70% of maximum protrusion, respectively. The highest risk of tooth movement occurred at the mandibular molar teeth. The mandibular second molar teeth had the highest risks of root and bone resorption. CONCLUSIONS: Mandibular advancement at 70% of maximum protrusion induces risks of tooth root resorption and bone resorption. The mandibular second molars were subjected to the highest stresses. Stress on the teeth and facial bones was the lowest at 40% of maximum mandibular advancement.

Effects of moderate intensity static magnetic fields on osteoclastic differentiation in mouse bone marrow cells.

Although we recently demonstrated that static magnetic fields (SMFs) of 3, 15, and 50 mT stimulate osteoblastic differentiation, the effects of SMFs on osteoclastogenesis are still poorly understood. This study focused on the suppressive effects of SMFs on receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis and bone resorption. Direct SMFs inhibit RANKL-induced multinucleated osteoclast formation, tartrate-resistant acid phosphatase activity, and bone resorption in mouse bone marrow-derived macrophage cells. The conditioned medium from osteoblasts treated with SMFs also resulted in the inhibition of osteoclast differentiation as well as resorption. The RANKL-induced expression of osteoclast-specific transcription factors, such as c-Fos and NFATc1, was remarkably downregulated by SMF at 15 mT. In addition, SMF inhibited RANKL-activated Akt, glycogen synthase kinase 3ß (GSK3ß), extracellular signal-regulated kinase, c-jun N-terminal protein kinase, mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) formation. These findings indicate that SMF-mediated attenuation of RANKL-induced Akt, GSK3ß, MAPK, and NF-κB pathways could contribute to the direct and indirect inhibition of osteoclast formation and bone resorption. Therefore, SMFs could be developed as a therapeutic agent against periprosthetic or peri-implant osteolysis. Additionally, these could be used against osteolytic diseases such as osteoporosis and rheumatoid arthritis. Bioelectromagnetics. 39:394-404, 2018. © 2018 Wiley Periodicals, Inc.

The Effect of Fibronectin-Immobilized Microgrooved Titanium Substrata on Cell Proliferation and Expression of Genes and Proteins in Human Gingival Fibroblasts.

BACKGROUND: We aimed to determine the effect of fibronectin (FN)-immobilized microgrooved titanium (Ti) on human gingival fibroblast proliferation, gene expression and protein expression. METHODS: Photolithography was used to fabricate the microgrooved Ti, and amine funtionalization (silanization) was used for FN immobilization on titanium surfaces. Cell proliferation, gene expression and protein expression were analyzed, followed by multiple regression analysis for determining the influential factors on cell proliferation. RESULTS: FN-immobilized microgrooved Ti significantly enhanced the fibroblast proliferation in various timelines of culture, among which a burst of fivefold increase is induced at 96 h of culture compared to that on the control smooth Ti. We suggest a presence of the synergistic promotion effect of microgrooves and FN immobilization on fibroblast proliferation. Through a series of analyses on the expression of various genes and proteins involved in cell adhesion and proliferation, cyclin-dependent kinase 6, cyclin D1, integrin α5, oncogene c-Src, osteonectin, paxillin and talin-2 were determined as influential factors on promoting fibroblast proliferation induced by FN-immobilized microgrooved Ti. CONCLUSION: FN-immobilized microgrooved Ti can act as an effective surface for enhancing fibroblast proliferation, and can be used for promoting soft tissue response on the connective tissue attachment zone of biomaterial surfaces.

Analysis of dimensions and shapes of maxillary and mandibular dental arch in Korean young adults.

PURPOSE: The aim of this study was to investigate dental arch dimensions and to classify arch shape in Korean young adults. MATERIALS AND METHODS: The sample included 50 Koreans with age ranging from 24 to 32 years. Maxillary and mandibular casts were fabricated using irreversible hydrocolloid and type III dental stones. Incisor-canine distance, incisor-1st molar distance, incisor-2nd molar distance, intercanine distance, inter-1st molar distance, and inter-2nd molar distance in both the maxillary and mandibular arch were measured using a three-dimensional measuring device. The dental arch was classified into three groups using five ratios from the measured values by the K-means clustering method. The data were analyzed with one-way analysis of variance. RESULTS: Arch lengths (IM2D, incisal-2nd molar distance) were 44.13 mm in the maxilla and 40.40 mm in the mandible. Arch widths (M2W, inter 2nd molar width) were 64.12 mm in the maxilla and 56.37 mm in the mandible. Distribution of the dental arch form was mostly ovoid shape (maxilla 52% and mandible 56%), followed by the V-shape and the U-shape. The arch width for the U-shape was broader than for the other forms. CONCLUSION: This study establishes new reference data for dental arch dimensions for young Korean adults. The most common arch form is the ovoid type in the maxilla and mandible of Koreans. Clinicians should be aware of these references and classify arch type before and during their dental treatment for effective and harmonized results in Koreans.

Static magnetic fields promote osteoblastic/cementoblastic differentiation in osteoblasts, cementoblasts, and periodontal ligament cells.

PURPOSE: Although static magnetic fields (SMFs) have been used in dental prostheses and osseointegrated implants, their biological effects on osteoblastic and cementoblastic differentiation in cells involved in periodontal regeneration remain unknown. This study was undertaken to investigate the effects of SMFs (15 mT) on the osteoblastic and cementoblastic differentiation of human osteoblasts, periodontal ligament cells (PDLCs), and cementoblasts, and to explore the possible mechanisms underlying these effects. METHODS: Differentiation was evaluated by measuring alkaline phosphatase (ALP) activity, mineralized nodule formation based on Alizarin red staining, calcium content, and the expression of marker mRNAs assessed by reverse transcription polymerase chain reaction (RT-PCR). Signaling pathways were analyzed by western blotting and immunocytochemistry. RESULTS: The activities of the early marker ALP and the late markers matrix mineralization and calcium content, as well as osteoblast- and cementoblast-specific gene expression in osteoblasts, PDLCs, and cementoblasts were enhanced. SMFs upregulated the expression of Wnt proteins, and increased the phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) and total ß-catenin protein expression. Furthermore, p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) pathways were activated. CONCLUSIONS: SMF treatment enhanced osteoblastic and/or cementoblastic differentiation in osteoblasts, cementoblasts, and PDLCs. These findings provide a molecular basis for the beneficial osteogenic and/or cementogenic effect of SMFs, which could have potential in stimulating bone or cementum formation during bone regeneration and in patients with periodontal disease.

Analysis of crown size and morphology, and gingival shape in the maxillary anterior dentition in Korean young adults.

PURPOSE: The aim of this investigation was to analyze the dimensions of clinical crowns and to classify the crown and the gingival type in the anterior teeth in Korean young adults. MATERIALS AND METHODS: Casts were obtained from 50 subjects ranging in age from 24 to 32. Measurements of length and width were made on the casts using a pair of digital calipers on the entire dentition. Crown thickness and papilla height were also measured and MDW/CL (mesiodistal width to clinical length) and CW/CL (cervical width to clinical length) ratios of the maxillary anterior teeth were calculated. The K-clustering method was used for CW/CL to classify the anterior tooth shape into three groups (tapered, ovoid, and square), and one-way analysis of variance and Duncan's post-hoc comparison were used to evaluate statistical significance between the groups. Pearson's correlation analysis was performed between tooth shape and papillary height (PH) to demonstrate the correlation between tooth shape and gingival morphological characteristics. RESULTS: The average length of the maxillary central incisors was 9.89 mm; the mesio-distal width was 8.54 mm; and the ratio of width/length was 0.86 in Korean young adults. The average bucco-palatal thickness of the central incisor was 3.14 mm at the incisal 1/3 aspect. Ovoid type was the most common tooth shape (48%), followed by square type (29%) and taper type (23%) in the central incisors of Korean young adults. Tooth shape and gingival type were correlated with each other. CONCLUSION: New reference data were established for tooth size in Korean young adults and the data show several patterns of tooth shape and gingival type. Clinicians should diagnose and treat based on these characteristics for better results in the Korean population.

Characterization and structure-activity relationship study of iminodipyridinopyrimidines as novel hepatitis C virus inhibitor.

Upon high-throughput screening of synthetic small molecule libraries with the infectious hepatitis C virus (HCV) cell culture system, we identified an iminodipyridinopyrimidine (IDPP) scaffold. IDPP did not inhibit HCV replication, but exhibited very potent inhibitory activity on early and late steps of HCV life cycle. Applying an intensive structure-activity relationship (SAR) study, a promising IDPP Lead compound (12c) with excellent potency (EC50 = 10 nM), high safety margin (SI > 2000), and an acceptable stability in human and rat liver microsomes (t1/2 >60 min) was identified. Overall, our results suggest that the IDPP scaffold could be used for the development of novel HCV interventions.

Reliability of a CAD/CAM Surgical Guide for Implant Placement: An In Vitro Comparison of Surgeons' Experience Levels and Implant Sites.

PURPOSE: This in vitro study evaluated the reliability of a surgical guide with regard to different levels of operator surgical experience and implant site. MATERIALS AND METHODS: A stereolithographic surgical guide for epoxy resin mandibles with three edentulous molar sites was produced using a computer-aided design/computer-assisted manufacture (CAD/CAM) system. Two surgeons with and two surgeons without implant surgery experience placed implants in a model either using or not using the CAD/CAM surgical guide. Four groups were created: inexperienced surgeon without the guide (group 1); experienced surgeon without the guide (group 2); inexperienced surgeon with the guide (group 3); and experienced surgeon with the guide (group 4). Planned implants and placed implants were superimposed using digital software, and deviation parameters were calculated. RESULTS: There were no significant differences in any of the deviation parameters between the groups when using the surgical guide. With respect to the implant sites, there were no significant differences among the groups in any parameter. CONCLUSION: Use of the CAD/CAM surgical guide reduced discrepancies among operators performing implant surgery regardless of their level of experience. Whether or not the guide was used, differences in the anterior-posterior implant site in the molar area did not affect the accuracy of implant placement.

Enhanced detection sensitivity of carcinoembryonic antigen on a plasmonic nanoimmunosensor by transmission grating-based total internal reflection scattering microscopy.

Carcinoembryonic antigen (CEA) is a glycoprotein associated with colorectal carcinomas and is commonly used as a clinical tumor marker. Enhanced detection sensitivity for the assay of CEA molecules was achieved on a plasmonic nanoimmunosensor by wavelength-dependent transmission grating (TG)-based total internal reflection scattering microscopy (TIRSM). The plasmonic nanoparticles were placed in an evanescent field layer on a glass nanoimmunosensor that produced evanescent wave scattering by the total internal reflection of light from two lasers. The light scattered by target protein (CEA)-bound 20-nm silver nanoparticles (plasmonic nanoprobes) was collected and spectrally isolated in first-order spectral images (n=+1) by a TG (70 grooves/mm). The combination of evanescent wave scattering and TG ​significantly enhanced the detection sensitivity and selectivity due to the minimized spectroscopic interference and background noise. The TG-TIRSM method detected the CEA molecules at concentrations down to 19.75zM with a wide linear dynamic range of 19.75zM-39.50nM (correlation coefficient, R=0.9903), which was 45 to 1.25×109 times lower than the detection limits and 2×105 to 2×1011 times wider than the dynamic ranges of previous assay methods. In particular, by simply changing the antibody of the target molecule, this technique can be used to detect various disease-related protein biomarkers directly in human biological samples at the single-molecule level.