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Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods. When applied to tobacco use phenotypes, TESLA identified 273 new genes, up to 55% more compared with alternative TWAS methods. These hits and subsequent fine mapping using TESLA point to target genes with biological relevance. In silico drug-repurposing analyses highlight several drugs with known efficacy, including dextromethorphan and galantamine, and new drugs such as muscle relaxants that may be repurposed for treating nicotine addiction.

BackgroundSubstance use occurs at a high rate in persons with a psychiatric disorder. Genetically informative studies have the potential to elucidate the etiology of these phenomena. Recent developments in genome-wide association studies (GWAS) allow new avenues of investigation.MethodUsing results of GWAS meta-analyses, we performed a factor analysis of the genetic correlation structure, a genome-wide search of shared loci, and causally informative tests for six substance use phenotypes (four smoking, one alcohol, and one cannabis use) and five psychiatric disorders (ADHD, anorexia, depression, bipolar disorder, and schizophrenia).ResultsTwo correlated externalizing and internalizing/psychosis factor were found, although model fit was beneath conventional standards. Of 458 loci reported in previous univariate GWAS of substance use and psychiatric disorders, about 50% (230 loci) were pleiotropic with additional 111 pleiotropic loci not reported from past GWAS. Of the 341 pleiotropic loci, 152 were associated with both substance use and psychiatric disorders, implicating neurodevelopment, cell morphogenesis, biological adhesion pathways, and enrichment in 13 different brain tissues. Seventy-five and 114 pleiotropic loci were specific to either psychiatric disorders or substance use phenotypes, implicating neuronal signaling pathway and clathrin-binding functions/structures, respectively. No consistent evidence for phenotypic causation was found across different Mendelian randomization methods.ConclusionsGenetic etiology of substance use and psychiatric disorders is highly pleiotropic and involves shared neurodevelopmental path, neurotransmission, and intracellular trafficking. In aggregate, the patterns are not consistent with vertical pleiotropy, more likely reflecting horizontal pleiotropy or more complex forms of phenotypic causation.

Salmonella is one of the major causes of food-borne infections. We investigated the serotype distribution and antimicrobial resistance of Salmonella isolates collected in Korea between January 2016 and December 2017. In total, 669 Salmonella isolates were collected from clinical specimens at 19 university hospitals. Serotyping was performed according to the Kauffmann-White scheme, and antimicrobial susceptibility was tested using Sensititre EUVSEC plates or disk diffusion. Among the strains, C (39.8%) and B (36.6%) were the most prevalent serogroups. In total, 51 serotypes were identified, and common serotypes were S. enterica serovar I 4,[5],12:i:- (16.7%), S. Enteritidis (16.1%), S. Bareilly (14.6%), S. Typhimurium (9.9%), and S. Infantis (6.9%). The resistance rates to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole were 32.6%, 12.1%, and 8.4%, respectively. The resistance rates to cefotaxime and ciprofloxacin were 8.1% and 3.0%, respectively, while 5.4% were multidrug-resistant. S. enterica serovar I 4,[5],12:i:- and S. Enteritidis were highly prevalent, and there was an increase in rare serotypes. Multidrug resistance and ciprofloxacin resistance were highly prevalent. Periodic investigations of Salmonella serotypes and antimicrobial resistance are needed.

Maclura tricuspidata, which belongs to the Moraceae family, is widely distributed in Asia, including Korea. All parts of this plant, such as roots, fruits, and leaves, are rich in diverse bioactive compounds, especially xanthones and isoflavonoids. Investigation of the leaves of M. tricuspidata through various chromatographic techniques yielded fourteen compounds, including five new compounds. The new compounds were determined to comprise an isoflavonoid structure with hydroxyethyl moiety and defined as hydroxyethylisoflavones A-E (10-14) on the basis of 1D and 2D NMR and MS data. These compounds efficiently inhibited α-glucosidase activity.

Background: An activating mutation (c.617A>C/p.Lys206Arg, L206R) in protein kinase cAMP-activated catalytic subunit alpha (PRKACA) has been reported in 35% to 65% of cases of cortisol-producing adenomas (CPAs). We aimed to compare the clinical characteristics and transcriptome analysis between PRKACA L206R mutants and wild-type CPAs in Korea.Methods: We included 57 subjects with CPAs who underwent adrenalectomy at Seoul National University Hospital. Sanger sequencing for PRKACA was conducted in 57 CPA tumor tissues. RNA sequencing was performed in 13 fresh-frozen tumor tissues.Results: The prevalence of the PRKACA L206R mutation was 51% (29/57). The mean age of the study subjects was 42±12 years, and 87.7% (50/57) of the patients were female. Subjects with PRKACA L206R mutant CPAs showed smaller adenoma size (3.3±0.7 cm vs. 3.8±1.2 cm, P=0.059) and lower dehydroepiandrosterone sulfate levels (218±180 ng/mL vs. 1,511±3,307 ng/mL, P=0.001) than those with PRKACA wild-type CPAs. Transcriptome profiling identified 244 differentially expressed genes (DEGs) between PRKACA L206R mutant (n=8) and wild-type CPAs (n=5), including five upregulated and 239 downregulated genes in PRKACA L206R mutant CPAs (|fold change| ≥2, PCTNNB1 was the most significant transcription regulator. In several pathway analyses, the Wnt signaling pathway was downregulated and the steroid biosynthesis pathway was upregulated in PRKACA mutants. Protein-protein interaction analysis also showed that PRKACA downregulates Wnt signaling and upregulates steroid biosynthesis.Conclusion: The PRKACA L206R mutation in CPAs causes high hormonal activity with a limited proliferative capacity, as supported by transcriptome profiling.

Supermealworm, Zophobas atratus (Coleoptera: Tenebrionidae) is a tropical species used for human consumption and as an ingredient in animal feed. We investigated the hatching characteristics of Z. atratus eggs under varying conditions to optimize artificial rearing conditions. Overall, the average egg weight, width, and length decreased by 42.3%, 3.7%, and 10.1%, respectively, on the 6th day post-oviposition. We varied either temperature, photoperiod, illuminance, or humidity, while the other conditions remained constant. Of the four experimental temperatures—25 °C, 27 °C, 30 °C, and 33 °C–30 °C was associated with the highest hatching rate (91.0%) during days 5–7. Although other experimental conditions did not have a significant effect on hatchability, we were able to elucidate the ideal conditions for improved hatchability. For photoperiod, hatchability was the highest (84%) at 12L/12D, followed by 81.0% at 15L/9D, and 70% at 9L/15D. Among the illuminance conditions tested—600, 1800, and 3000 lx—hatchability was the highest at 1800 lx (82.3% on days 4–6). Among the relative humidity (RH) levels tested—50%, 65%, and 80%—hatchability was the highest at 65% RH (88.5% on days 5–6). Thus, the ideal conditions for maximum hatchability were 30 °C, 12L/12D, 65% RH, and 1800 lx. Under these combined conditions, the hatching rate increased by 93.6%, and the hatching time was reduced by two days.

Remodeling of mitochondrial dynamics and mitochondrial morphology plays a pivotal role in the maintenance of mitochondrial homeostasis in response to pathogenic attacks or stress stimuli. In addition to their role in metabolism and energy production, mitochondria participate in diverse biological functions, including innate immune responses driven by macrophages in response to infections or inflammatory stimuli. Mitofusin-2 (MFN2), a mitochondria-shaping protein regulating mitochondrial fusion and fission, plays a crucial role in linking mitochondrial function and innate immune responses. In this article, we review the role of MFN2 in the regulation of innate immune responses during viral and bacterial infections. We also summarize the current knowledge on the role of MFN2 in coordinating inflammatory, atherogenic, and fibrotic responses. MFN2-mediated crosstalk between mitochondrial dynamics and innate immune responses may determine the outcomes of pathogenic infections.

Metal–organic framework (MOF) nanoparticles are promising carriers for the internal delivery of therapeutics to the cells; however, the effects of their shape on cellular uptake have not yet been clearly evaluated. Therefore, we synthesized biocompatible Fe-based MOF nanoparticles of two distinct shapes—rods and octahedrons (NH2-MIL-88B(Fe)-ROD and NH2-MIL-88B(Fe)-OCTA, respectively)—and evaluated their cellular uptake kinetics and mechanisms using three different cell lines (HeLa, MDA-MB-231, and L929). Although both nanoparticles possessed the same constituent metal, organic linkers, and thus, crystalline structures, a more rapid uptake was observed with NH2-MIL-88B(Fe)-OCTA, whereas NH2-MIL-88B(Fe)-ROD were endocytosed in a more sustained manner. This could be ascribed to the large number of sharp edges available in NH2-MIL-88B(Fe)-OCTA particles; hence, there were more points of expedited entry into the cells via a clathrin-mediated pathway. The findings herein provide important information for the application of the MOF nanoparticles as intracellular drug delivery carriers, especially when they can be prepared in different shapes with the same composition.

Silver nanoparticles (AgNPs) have various industrial applications; however, when released into wastewater, AgNPs have significant effects on aquatic ecosystems. Silver nanowaste materials in aquatic ecosystems could be conjugated and removed using jellyfish immune reaction extract (JEIs). In this study, we investigate the biological effects of JEIs and JEIs with silver nanoparticles (AgNPs) on zebrafish embryogenesis and aquatic bacteria. JEIs were extracted using two methods, a previously established method (AJEI) and the new JEI extraction method (BJEI). BJEI bound 96.64% (2 mg/L) of nano-Ag-citrate (AgN-Citrate) and 96.17% of nano-Ag-polyvinyl-pyrrolidone (AgN-PVP) 1 h following exposure, and significantly reduced the toxic effect of AgNPs on zebrafish embryos to a greater extent than AJEI, extracted using the previous method. However, upon exposure to BJEI, the number of viable aquatic bacteria was reduced owing to the antibacterial effects of JEI. JEIs captured Ag-citrate NPs and AgN-PVP and reduced their nano-toxicity. The BJEI extraction method resulted in lower toxicity for zebrafish embryogenesis, as copmared to that with AJEI. JEI has antibacterial effects; however, information on the specific targets of the antibacterial materials is scarce. JEI did not accumulate or persist since it is a reaction material from the jellyfish and degraded in aquatic environments. Therefore, BJEI can be a promising material for removing AgNPs from aquatic ecosystems.

Bacillus is characterized by the formation of spores in harsh environments, which makes it suitable for use as a probiotic for feed because of thermostability and high survival rate, even under long-term storage. This study was conducted to investigate the effects of Bacillus-based probiotics on growth performance, nutrient digestibility, intestinal morphology, immune response, and intestinal microbiota of weaned pigs. A total of 40 weaned pigs (7.01 ± 0.86 kg body weight [BW]; 28 d old) were randomly assigned to two treatments (4 pigs/pen; 5 replicates/treatment) in a randomized complete block design (block = BW and sex). The dietary treatment was either a typical nursery diet based on corn and soybean meal (CON) or CON supplemented with 0.01% probiotics containing a mixture of Bacillus subtilis and Bacillus licheniformis (PRO). Fecal samples were collected daily by rectal palpation for the last 3 days after a 4-day adaptation. Blood, ileal digesta, and intestinal tissue samples were collected from one pig in each pen at the respective time points. The PRO group did not affect the feed efficiency, but the average daily gain was significantly improved (p < 0.05). The PRO group showed a trend of improved crude protein digestibility (p < 0.10). The serum transforming growth factor-β1 level tended to be higher (p < 0.10) in the PRO group on days 7 and 14. There was no difference in phylum level of the intestinal microbiota, but there were differences in genus composition and proportions. However, β-diversity analysis showed no statistical differences between the CON and the PRO groups. Taken together, Bacillus-based probiotics had beneficial effects on the growth performance, immune system, and intestinal microbiota of weaned pigs, suggesting that Bacillus can be utilized as a functional probiotic for weaned pigs.

The SARS-CoV-2 variant is rapidly spreading across the world and causes to resurge infections. We previously reported that CT-P59 presented its in vivo potency against Beta variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on Gamma, Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal studies. CT-P59 showed neutralization against Gamma, Delta, Epsilon, and Kappa variants in cells, with reduced susceptibility. The mouse challenge experiments with Gamma and Delta variants substantiated in vivo potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against Gamma and Delta variants infection, hinting that CT-P59 has therapeutic potential for patients infected with Gamma, Delta and its associated variants.

BackgroundRecent well-powered genome-wide association studies have enhanced prediction of substance use outcomes via polygenic scores (PGSs). Here, we test (1) whether these scores contribute to prediction over-and-above family history, (2) the extent to which PGS prediction reflects inherited genetic variation v. demography (population stratification and assortative mating) and indirect genetic effects of parents (genetic nurture), and (3) whether PGS prediction is mediated by behavioral disinhibition prior to substance use onset.MethodsPGSs for alcohol, cannabis, and nicotine use/use disorder were calculated for Minnesota Twin Family Study participants (N = 2483, 1565 monozygotic/918 dizygotic). Twins' parents were assessed for histories of substance use disorder. Twins were assessed for behavioral disinhibition at age 11 and substance use from ages 14 to 24. PGS prediction of substance use was examined using linear mixed-effects, within-twin pair, and structural equation models.ResultsNearly all PGS measures were associated with multiple types of substance use independently of family history. However, most within-pair PGS prediction estimates were substantially smaller than the corresponding between-pair estimates, suggesting that prediction is driven in part by demography and indirect genetic effects of parents. Path analyses indicated the effects of both PGSs and family history on substance use were mediated via disinhibition in preadolescence.ConclusionsPGSs capturing risk of substance use and use disorder can be combined with family history measures to augment prediction of substance use outcomes. Results highlight indirect sources of genetic associations and preadolescent elevations in behavioral disinhibition as two routes through which these scores may relate to substance use.

Observational studies have repeatedly linked cannabis use and increased risk of psychosis. We sought to clarify whether this association reflects a causal effect of cannabis exposure or residual confounding. We analyzed data from two cohorts of twins who completed repeated, prospective measures of cannabis use (N = 1544) and cannabis use disorder symptoms (N = 1458) in adolescence and a dimensional measure of psychosis-proneness (the Personality Inventory for DSM-5 Psychoticism scale) in adulthood. Twins also provided molecular genetic data, which were used to estimate polygenic risk of schizophrenia. Both cumulative adolescent cannabis use and use disorder were associated with higher Psychoticism scores in adulthood. However, we found no evidence of an effect of cannabis on Psychoticism or any of its facets in co-twin control models that compared the greater-cannabis-using twin to the lesser-using co-twin. We also observed no evidence of a differential effect of cannabis on Psychoticism by polygenic risk of schizophrenia. Although cannabis use and disorder are consistently associated with increased risk of psychosis, the present results suggest this association is likely attributable to familial confounds rather than a causal effect of cannabis exposure. Efforts to reduce the prevalence and burden of psychotic illnesses thus may benefit from greater focus on other therapeutic targets. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

In this study, suitable protectants and rehydration solutions were investigated for the development of ‘Yakju’ yeast starters. Experiments were conducted alongside the optimization of protectant and rehydration conditions using different types of sugars and rehydration solutions to enhance the viability and storability of air-blast dried yeast cells. Six types of sugars (fructose, glucose, maltose, raffinose, sucrose, trehalose) and four types of rehydration solutions (DW, PBS, 0.85% NaCl, and 1% peptone water) were examined to investigate optimal air-blast drying conditions to enhance the survival rate of Saccharomyces yeasts cells. 10% sucrose (DW) and 10% maltose (PBS) had the highest survival rate of 108.20% and 107.72% for S. cerevisiae W153 and W149, respectively. we assumed that the increased survival rate (>100%) was as a result of the re-initiation of the proliferation of the air-blast dried yeast cells during the 1-h rehydration. We also investigated physicochemical properties as well as sensory quality of ‘Yakju’. S. cerevisiae W153 and W149 showed good alcohol fermentation ability in the three different raw materials such as glutinous rice only (Glu 100), non-glutinous rice (NGlu 100), glutinous and non-glutinous rice mixture (NGlu 50:50). The sensory evaluation revealed that S. cerevisiae W153 obtained the highest scores in the flavor as well as the overall preference with the Glu 100.

The complete chloroplast (cp) genome sequence of Neolitsea sericea was determined by Illumina sequencing. The complete cp genome was 152,446bp in length, containing a large single-copy region of 93,796 bp and a small single-copy region of 18,506bp, which were separated by a pair of 20,072bp inverted repeats. A total of 112 unique genes were annotated, including 78 protein-coding genes (PCGs), 30 transfer RNAs, and four ribosomal RNAs. Among the PCGs, 18 genes contained one or two introns. A very low level of sequence variation between two cp genomes of N. sericea was found with seven insertions or deletions and only one single nucleotide polymorphism. An analysis using the maximum likelihood method showed that N. sericea was closely related to Actinodaphne trichocarpa.

Two aphid-transmitted RNA viruses, broad bean wilt virus 2 (BBWV2) and cucumber mosaic virus (CMV), are the most prevalent viruses in Korean pepper fields and cause chronic damage in pepper production. In this study, we employed a screening system for pathotype-specific resistance of pepper germplasm to BBWV2 and CMV by utilizing infectious cDNA clones of different pathotypes of the viruses (two BBWV2 strains and three CMV strains). We first examined pathogenic characteristics of the BBWV2 and CMV strains in various plant species and their phylogenetic positions in the virus population structures. We then screened 34 commercial pepper cultivars and seven accessions for resistance. While 21 pepper cultivars were resistant to CMV Fny strain, only two cultivars were resistant to CMV P1 strain. We also found only one cultivar partially resistant to BBWV2 RP1 strain. However, all tested commercial pepper cultivars were susceptible to the resistance-breaking CMV strain GTN (CMV-GTN) and BBWV2 severe strain PAP1 (BBWV2-PAP1), suggesting that breeding new cultivars resistant to these virus strains is necessary. Fortunately, we identified several pepper accessions that were resistant or partially resistant to CMV-GTN and one symptomless accession despite systemic infection with BBWV2-PAP1. These genetic resources will be useful in pepper breeding programs to deploy resistance to BBWV2 and CMV.

Freshwater-dominated estuaries experience large fluctuations in their physical and chemical environments which may influence larval dispersal, settlement, and connectivity of populations with pelagic larval stages. We used settlement patterns and natural tagging along with numerical hydrodynamic model results to assess settlement and connectivity among oysters across the freshwater-dominated Mobile Bay-eastern Mississippi Sound (MB-EMS) system. Specifically, we (1) tested how freshwater inputs and associated environmental attributes influenced settlement patterns during high and low discharge conditions in 2014 and 2016, respectively, and (2) analyzed trace element (TE) ratios incorporated into multiple shell types (larval and settled shell of spat and adult shells) to determine if shells collected in situ incorporate temporally stable site-specific signatures. We also assessed if TE ratios compared between adult (TE natal signature proxy) and larval shells could infer connectivity. Larval settlement was 4× higher during low discharge than during high discharge when oyster larvae only settled in higher salinity regions (EMS). Spat and adult shells incorporated site-specific TE ratios that varied from weeks to months. Connectivity results (May-June 2016 only) suggest that EMS is an important larval source to EMS and lower MB. While we were able to infer probable connectivity patterns using adult and larval shells, more study is needed to assess the utility of adult shells as proxies for natal-location TE signatures. Results provide a baseline for measuring future larval connectivity and adult distribution changes in the MB-EMS system. Biological and geochemical data demonstrate the potential to identify environmental attributes that spatiotemporally mediate settlement and connectivity in dynamic systems.

The ongoing coronavirus disease-2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus-2. COVID-19 severity is related to the cytokine storm phenomenon, which is amplified by pro-inflammatory cytokines and chemokines;it may cause extensive pulmonary damage. Among these cytokines, interleukin (IL)-17, produced mainly by T helper 17 (Th17) cells, is responsible for the immunopathological responses present in acute respiratory distress syndrome. This review discusses the roles of IL-17 and Th17 responses in the pathophysiology of COVID-19. Dysregulated Th17-responses, linked to various risk factors, may contribute to pathological inflammation through the amplification of multiple inflammatory cytokines and chemokines, as well as augmentation of neutrophil infiltration in the lungs of severe COVID-19 patients. A more detailed understanding of the roles of Th17 responses, as well as the mechanisms underlying altered IL-17 production and signaling, may improve therapeutic strategies for severe or critically ill COVID-19 patients by targeting the IL-17 pathway. © 2021 Journal of Bacteriology and Virology.

I-motif or C4 is a four-stranded DNA structure with a protonated cytosine:cytosine base pair (C+:C) found in cytosine-rich sequences. We have found that oligodeoxynucleotides containing adenine and cytosine repeats form a stable secondary structure at a physiological pH with magnesium ion, which is similar to i-motif structure, and have named this structure ‘adenine:cytosine-motif (AC-motif)’. AC-motif contains C+:C base pairs intercalated with putative A+:C base pairs between protonated adenine and cytosine. By investigation of the AC-motif present in the CDKL3 promoter (AC-motifCDKL3), one of AC-motifs found in the genome, we confirmed that AC-motifCDKL3 has a key role in regulating CDKL3 gene expression in response to magnesium. This is further supported by confirming that genome-edited mutant cell lines, lacking the AC-motif formation, lost this regulation effect. Our results verify that adenine-cytosine repeats commonly present in the genome can form a stable non-canonical secondary structure with a non-Watson–Crick base pair and have regulatory roles in cells, which expand non-canonical DNA repertoires.

The three-dimensional organization of chromatin and its time-dependent changes greatly affect virtually every cellular function, especially DNA replication, genome maintenance, transcription regulation, and cell differentiation. Sequencing-based techniques such as ChIP-seq, ATAC-seq, and Hi-C provide abundant information on how genomic elements are coupled with regulatory proteins and functionally organized into hierarchical domains through their interactions. However, visualizing the time-dependent changes of such organization in individual cells remains challenging. Recent developments of CRISPR systems for site-specific fluorescent labeling of genomic loci have provided promising strategies for visualizing chromatin dynamics in live cells. However, there are several limiting factors, including background signals, off-target binding of CRISPR, and rapid photobleaching of the fluorophores, requiring a large number of target-bound CRISPR complexes to reliably distinguish the target-specific foci from the background. Various modifications have been engineered into the CRISPR system to enhance the signal-to-background ratio and signal longevity to detect target foci more reliably and efficiently, and to reduce the required target size. In this review, we comprehensively compare the performances of recently developed CRISPR designs for improved visualization of genomic loci in terms of the reliability of target detection, the ability to detect small repeat loci, and the allowed time of live tracking. Longer observation of genomic loci allows the detailed identification of the dynamic characteristics of chromatin. The diffusion properties of chromatin found in recent studies are reviewed, which provide suggestions for the underlying biological processes.

The Ulleungdo and Dokdo Islands are located in the East Sea of Korea and have a unique ecosystem. We collected Aphidiinae mummies from the Ulleungdo and Dokdo Islands in 2018. Three species of parasitoids in the genus Aphidius Nees, A. absinthii Marshall, A. areolatus Ashmead, and A. uzbekistanicus Luzhetzki, were identified using morphological characteristics and molecular techniques from the mummies of three aphid host species Macrosiphoniella formosartemisiae Takahashi, Capitophorus elaeagni (Del Guercio), and Aphis rumicis Linnaeus, respectively. The comparison of the nucleotide sequences of mitochondrial cytochrome c oxidase subunit I in the GenBank database revealed that A. uzbekistanicus was 100% identical to 135 sequences of the species from Asian, American, and European countries and a one-nucleotide variation from a Serbian specimen. Aphidius absinthii was 100% identical to a Japanese specimen of the species and 0.39% variable from the Serbian specimen. However, the cytochrome c oxidase subunit I sequence of A. areolatus did not match in the database and was first reported from this study. Our phylogenetic analysis of 31 Aphidius and 3 Euaphidius species listed in the GenBank database indicated a monophyletic taxon within 12.72% variation. This study is the first report of the geographic distribution of three Aphidius species in the Ulleungdo and Dokdo Islands of Korea.

Polo-like kinase-1 (Plk1) plays a key role in mitosis and has been identified as an attractive anticancer drug target. Plk1 consists of two drug-targeting sites, namely, N-terminal kinase domain (KD) and C-terminal polo-box domain (PBD). As KD-targeting inhibitors are associated with severe side effects, here we report on the pyrazole-based Plk1 PBD inhibitor, KBJK557, which showed a remarkable in vitro anticancer effect by inducing Plk1 delocalization, mitotic arrest, and apoptosis in HeLa cells. Further, in vivo optical imaging analysis and antitumorigenic activities in mouse xenograft models demonstrate that KBJK557 preferentially accumulates in cancer cells and selectively inhibits cancer cell proliferation. Pharmacokinetic profiles and partition coefficients suggest that KBJK557 was exposed in the blood and circulated through the organs with an intermediate level of clearance (t(1/2), 7.73 h). The present investigation offers a strategy for specifically targeting cancer using a newly identified small-molecule inhibitor that targets the Plk1 PBD.

Phytochemical investigation on the dried fruits of Casearia grewiifolia led to the identification of 10 new salicinoyl quinic acid derivatives (1-10), a new benzoyl quinic acid (11), and two known compounds (12 and 13). The structures of the new compounds were elucidated by interpreting 1D and 2D NMR spectroscopic data including HMBC and EXSIDE along with a chemical method for sugar unit analysis. All isolates were evaluated for their inhibitory activities against prostaglandin E2 (PGE2) production in ultraviolet B (UVB)-irradiated HaCat keratinocytes. Of the isolates tested, compounds 6 and 12 were found to inhibit PGE2 production with IC50 values of 20.5 and 28.8 μM, respectively.