Genetic Diversity and Population Structure of Rhodeus uyekii in the Republic of Korea Revealed by Microsatellite Markers from Whole Genome Assembly.

This study is the first report to characterize the Rhodus uyekii genome and study the development of microsatellite markers and their markers applied to the genetic structure of the wild population. Genome assembly was based on PacBio HiFi and Illumina HiSeq paired-end sequencing, resulting in a draft genome assembly of R. uyekii. The draft genome was assembled into 2652 contigs. The integrity assessment of the assemblies indicates that the quality of the draft assemblies is high, with 3259 complete BUSCOs (97.2%) in the database of Verbrata. A total of 31,166 predicted protein-coding genes were annotated in the protein database. The phylogenetic tree showed that R. uyekii is a close but distinct relative of Onychostoma macrolepis. Among the 10 fish genomes, there were significant gene family expansions (8-2387) and contractions (16-2886). The average number of alleles amplified by the 21 polymorphic markers ranged from 6 to 23, and the average PIC value was 0.753, which will be useful for evolutionary and genetic analysis. Using population genetic analysis, we analyzed genetic diversity and the genetic structures of 120 individuals from 6 populations. The average number of alleles per population ranged from 7.6 to 9.9, observed heterozygosity ranged from 0.496 to 0.642, and expected heterozygosity ranged from 0.587 to 0.783. Discriminant analysis of principal components According to the analysis method, the population was divided into three populations (BS vs. DC vs. GG, GC, MS, DC). In conclusion, our study provides a useful resource for comparative genomics, phylogeny, and future population studies of R. uyekii.

Changes in dental hygiene students' working posture following digital sound feedback.

INTRODUCTION: This study aimed to observe changes in working posture by measuring the REBA (Rapid Entire Body Assessment) score of dental hygiene students according to digital sound feedback linked with a smartphone application. METHODS: This study was conducted on 28 fourth-year dental hygiene students who received theoretical and practical training on dental posture in the second year and then practised on mannequins and patients for about four semesters. Periodontal instrumentation was performed freely by applying digital sound notification feedback for four weeks after baseline, 30 minutes per week. REBA was measured after performing periodic structure construction without providing digital sound notification feedback for the last 1-2 minutes. Follow-up was conducted the same way 2-3 weeks after the intervention period. RESULTS: The REBA score for total, neck and trunk of all subjects showed statistically significant decreases post-intervention compared with the baseline scores (total p < .001, neck p < .001 and trunk p = .042). CONCLUSIONS: A digital sound feedback system was shown to be effective in encouraging correct working posture in dental hygiene students by helping them improve their REBA scores.

Research on dental plaque removal methods for efficient oral prophylaxis: With a focus on air polishing and rubber cup polishing.

OBJECTIVES: This study was conducted to compare the plaque control effectiveness of rubber cup polishing with that of air polishing during oral prophylaxis procedures and to investigate the effect of the order of air-polishing application on the efficiency of oral prophylaxis. METHODS: The study included adult patients (≥20 years of age) who had visited the dental clinic for oral prophylaxis. A total of 173 subjects were divided into three groups (scaling followed by rubber cup polishing, SR; scaling followed by air polishing, SA; and air polishing followed by scaling, AS) based on sex, age, oral health status, oral hygiene status, and indications and contraindications according to the oral prophylaxis method. The analysis of variance (ANOVA) was used to determine the difference in oral prophylaxis time, residual deposits rate, subjects and dental hygienist satisfaction. RESULTS: The total scaling time was shorter in the AS group (15.4 ± 6.9 minutes) than in the SA (18.7 ± 5.5 minutes) and SR groups (19.9 ± 6.2 minutes) (p < 0.05). The rate of residual deposits was significantly higher in the SR group than in the AS or SA groups (p < 0.05). The satisfaction level of dental hygienists was higher in the AS group (8.8 ± 1.0 points) and the SA group (8.4 ± 1.0 points) than in the SR group (6.2 ± 1.3 points). CONCLUSION: During oral prophylaxis, dental plaque removal using air polishing requires a relatively longer time when compared to rubber cup polishing, but it can better eliminate dental plaque. In addition, we found that dental plaque removal using air polishing prior to scaling reduced the total scaling time.

Assessment of the Genetic Diversity and Structure of the Korean Endemic Freshwater Fish Microphysogobio longidorsalis (Gobioninae) Using Microsatellite Markers: A First Glance from Population Genetics.

Microphysogobio longidorsalis is endemic to South Korea and inhabits small areas of the Namhangang, Bukhangang, and Imjingang Rivers in the Hangang River water system. Endemic species usually are more vulnerable than species with a wide distribution. Notably, there is a lack of basic conservation data for M. longidorsalis. We analyzed 19 microsatellite loci in six populations of M. longidorsalis in South Korea to characterize their population structure and genetic diversity. The genetic diversity of the microsatellites was 0.741-0.779, which is lower than that of other freshwater fishes. The pairwise genetic differentiation of microsatellite (FST) values ranged from 0.007 to 0.041, suggesting low genetic differentiation between the populations. The Jojongicheon stream population (CP) had an effective population size of <100. Therefore, conservation efforts are required to prevent inbreeding depression in M. longidorsalis. Discriminant analysis of principal components showed that the Hangang River water system would be a single management unit (MU). Our findings provide fundamental genetic insights for the formulation of conservation strategies for M. longidorsalis.

Design, synthesis, and biological evaluation of a series of resorcinol-based N-benzyl benzamide derivatives as potent Hsp90 inhibitors.

Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is responsible for the stabilization and maturation of many oncogenic proteins. Therefore, Hsp90 has emerged as an attractive target in the field of cancer chemotherapy. In this study, we report the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors. In particular, compound 30f shows a significant Hsp90α inhibitory activity with IC50 value of 5.3 nM and an excellent growth inhibition with GI50 value of 0.42 µM against non-small cell lung cancer cells, H1975. Compound 30f effectively reduces the expression levels of Hsp90 client proteins including Her2, EGFR, Met, Akt, and c-Raf. Consequently, compound 30f promotes substantial cleavages of PARP, Caspase 3, and Caspase 8, indicating that 30f induces cancer cell death via apoptotic pathway. Moreover, cytochrome P450 assay indicates that compound 30f has weak inhibitory effect on the activities of five major P450 isoforms (IC50 > 5 µM for 1A2, 2C9, 2C19, 2D6, and 3A), suggesting that clinical interactions between 30f and the substrate drugs of the five major P450 isoforms are not expected. Compound 30f also inhibits the tumor growth in a mouse xenograft model bearing subcutaneous H1975 without noticeable abnormal behavior and body weight changes. The immunostaining and western immunoblot analysis of EGFR, Met, Akt in xenograft tissue sections of tumor further demonstrate a good agreement with the in vitro results.

Chalcone-templated Hsp90 inhibitors and their effects on gefitinib resistance in non-small cell lung cancer (NSCLC).

The molecular chaperone Hsp90 has emerged as an attractive cancer therapeutic target due to its role in cellular homeostasis by modulating the stabilization and maturation of many oncogenic proteins. In this study, we designed and synthesized a series of Hsp90 inhibitors that hybridized NVP-AUY992 (2) and PU3 (3) in the chalcone scaffold using a structure-based approach. Our results indicate that compound 1g inhibited the proliferation of gefitinib-resistant non-small cell lung cancer (H1975) cells, downregulated the expression of client proteins of Hsp90 including EGFR, MET, Her2 and Akt, and up-regulated the expression of Hsp70. The compound 1g represents a new class of Hsp90 inhibitors with a chalcone structure. The design, synthesis, and evaluation of 1g are described herein.

Hsp90 inhibitor SY-016 induces G2/M arrest and apoptosis in paclitaxel-resistant human ovarian cancer cells.

The aim of the present study was to evaluate the in vitro effect of a heat shock protein (Hsp)90 inhibitor, SY-016, on the paclitaxel (PTX)-resistant human ovarian cancer cell line OVCAR-3PTX, and explore its mechanism of apoptosis. In the present study, SY-016 was used in combination with PTX to determine its effect on the cell proliferation and apoptosis of OVCAR-3PTX cells. The drug-resistant tumor cells were established in vitro by stepwise sequential exposure to increasing concentrations of PTX. The cell viability and cell cycle distribution were measured by MTT assay and flow cytometric analysis, respectively. The induction of apoptosis was measured by caspase-3 activity, DNA fragmentation and western blot analyses. The cell viability significantly decreased following treatment with PTX and SY-016 as compared with either drug alone. The DNA fragmentation assay revealed an induction of apoptosis. The results from the flow cytometric analysis revealed an increase in the percentage of cells in the G2/M phase. Downregulation of B-cell lymphoma (Bcl)-2, X-linked inhibitor of apoptosis protein, survivin, Akt, nuclear factor-κB and cyclin-dependent kinase 4, as well as upregulation of Bcl-2-associated X protein, were observed. SY-016 may contribute to the induction of apoptosis in OVCAR-3PTX cells. These results suggest that SY-016 in combination with PTX may be a beneficial chemotherapeutic strategy, particularly in patients with tumors refractory to PTX.

Targeting the entry region of Hsp90's ATP binding pocket with a novel 6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl amide.

The molecular chaperone Hsp90 plays an important role in cancer cell survival and proliferation by regulating the maturation and stabilization of numerous oncogenic proteins. Due to its potential to simultaneously disable multiple signaling pathways, Hsp90 has emerged as an attractive therapeutic target for cancer treatment. In this study, the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors are described. Among the synthetic compounds, 6,7-dihydrothieno [3,2-c]pyridin-5(4H)-yl amide 19 exhibits a remarkable binding affinity to the N-terminus of Hsp90 in a fluorescence polarization (FP) binding assay (IC50 = 50.3 nM). Furthermore, it effectively inhibits the proliferation of H1975 non-small cell lung cancer (NSCLC) and Skbr3 breast cancer cell lines with GI50 values of 0.31 µM and 0.11 µM, respectively. Compound 19 induces the degradation of the Hsp90 client proteins including EGFR, Her2, Met, c-Raf, and Akt, and consequently promotes apoptotic cancer cell death. Compound 19 also inhibits the growth of H1975 xenografts in NOD-scid IL2R gammanull mice without any apparent body-weight loss. The immunohistologic evaluation indicates that compound 19 decreases the expression of Akt in xenograft tumor tissue via an inhibition of the Hsp90 chaperon function. Additionally, the cytochrome P450 assay indicates that compound 19 has no effect on the activities of five major P450 isoforms (IC50 > 50 µM for 1A2, 2C9, 2C19, 2D6, and 3A), suggesting that clinical interactions between compound 19 and the substrate drugs of the five major P450 isoforms are not expected. Overall, compound 19 represents a new class of Hsp90 inhibitor with its 6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl-amide structure, and it has the therapeutic potential to overcome drug resistance in cancer chemotherapy.