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Simple Summary: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, but effective biomarkers has yet been developed. Here, we identified ATP1A1 as prognostic marker and therapeutic target via integrated analysis of DNA methylome and transcriptome of TNBC. These data will provide new insight into not only developing specific biomarker for TNBC but also understanding TNBC pathogenesis. Dysregulated DNA methylation in cancer is critical in the transcription machinery associated with cancer progression. Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, but no treatment targeting TNBC biomarkers has yet been developed. To identify specific DNA methylation patterns in TNBC, methyl-binding domain protein 2 (MBD) sequencing data were compared in TNBC and the three other major breast cancer subtypes. Integrated analysis of DNA methylation and gene expression identified a gene set showing a correlation between DNA methylation and gene expression. ATPase Na+/K+-transporting subunit alpha 1 (ATP1A1) was found to be specifically hypomethylated in the coding sequence (CDS) region and to show increased expression in TNBC. The Cancer Genome Atlas (TCGA) database also showed that hypomethylation and high expression of ATP1A1 were strongly associated with poor survival in patients with TNBC. Furthermore, ATP1A1 knockdown significantly reduced the viability and tumor-sphere formation of TNBC cells. These results suggest that the hypomethylation and overexpression of ATP1A1 could be a prognostic marker in TNBC and that the manipulation of ATP1A1 expression could be a therapeutic target in this disease. [ABSTRACT FROM AUTHOR]

Ticks are vectors of disease‐causing pathogens and are found on domestic and wild animals; thus, they are also vectors of significant human diseases. For this reason, pre‐emptive measures to prevent tick‐borne diseases are necessary in the form of exploring their major habitats, population increase period, and factors affecting their population growth, all of which indicate the purpose of this study. In the study, a variation of Haemaphysalis longicornis, a major vector of fever‐causing conditions, was statistically analyzed to identify the spatial and climatic factors affecting the time‐dependent variations of its population. The survey occurred in different habitats (grassland, mixed forest, deciduous forest, and coniferous forest) in South Korea. In addition, we fitted a phenology model by using a probability function to find the peak occurrence time annually. As a result, the numbers of adults and nymphs were found to be related to temperature and relative humidity and their population peaked at the end of May in all habitats except deciduous forests. This study is expected to provide information on habitat types, times, and climate patterns that require attention to help control H. longicornis populations. [ABSTRACT FROM AUTHOR]

Abstract This study explores the relationship between users and avatars, focusing on the degree of facial resemblance and the realism of fashion items as the main factors of avatar self-integration that affect consumers’ behavioral intentions. Through a contactless survey, this study empirically identified how avatar–user resemblance and fashion item realism influence consumers’ future spending intention on virtual fashion items and the continuous usage intention of the metaverse by mediating psychological identification. We also demonstrate the moderating role of users’ self-monitoring of the effect of avatar–user resemblance on psychological identification. We found a positive mediation role of psychological identification between avatar–user resemblance, fashion item realism, and users’ consumption intentions. Additionally, a higher self-monitoring tendency strengthens the positive effect of avatar–user resemblance on psychological identification. The study establishes an academic basis for metaverse retailing by uncovering connections between predictors contributing to users’ consumption intentions in the metaverse. [ABSTRACT FROM AUTHOR]

This study aimed to report a single surgeon's early experience and learning curves of single-incision robotic sacrocolpopexy on two different robotic surgical platforms, namely, the single-site approach on da Vinci Xi® and single-port approach on da Vinci SP® surgical systems. This retrospective study included 123 consecutive cases of robotic sacrocolpopexy performed between June 2017 and June 2021 for the patients with Pelvic Organ Prolapse Quantification stage 2–4 symptomatic prolapse. First consecutive 57 cases were performed under the da Vinci Xi® system applying the single-site manner, whereas the following 66 cases were done under the da Vinci SP® system. The primary outcome was intraoperative and perioperative complication rates, and the secondary outcome was learning curve of single-incision robotic sacrocolpopexy under the two different robotic surgical platforms. Learning curves based on the operation time were obtained through cumulative sum analysis. The mean age of each group was 65.6 ± 8.7 years for single-site robotic sacrocolpopexy and 63.7 ± 7.6 years for the single-port one (p = 0.202). More than 80% of patients for each group had advanced prolapse stages and underwent concomitant total hysterectomy. The overall baseline characteristics did not differ significantly between groups. The median operation time for each group were 201.0 and 201.5 min, respectively. Both groups showed comparable perioperative outcomes in terms of operation time, intraoperative blood loss, and length of hospital stay. Intraoperative cystostomy rates were 1.8% and 3.0%, respectively, and revealed no statistical difference (p = 0.736). The learning curves were comparable, and the surgeon required less than 15 cases for both single-site and single-port robotic sacrocolpopexies to stabilize operation time. Comparable learning curves and favorable intraoperative and perioperative outcomes of single-incision robotic sacrocolpopexy using two different robotic surgical systems show that both are feasible options for robotic sacrocolpopexy. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate a prediction model for bothersome stress urinary incontinence after prolapse surgery and to compare it with an existing clinical prediction model (CUPIDO model). Design: Retrospective cohort study. Setting: Two tertiary hospitals in South Korea. Population: A total of 1142 patients who underwent prolapse surgery with or without a concomitant midurethral sling. Methods: To construct a prediction model, we performed logistic regression using both exhaustive and stepwise variable selection, validating the model both internally and externally. Main Outcome Measures: Bothersome stress urinary incontinence defined as the presence of bothersome symptoms of stress urinary incontinence and/or subsequent continence procedure one year after surgery. Results: Postoperative bothersome stress urinary incontinence occurred in 10% of patients. A model containing six predictors (age, diabetes mellitus, subjective urinary incontinence, prolapse reduction stress test result, type of prolapse surgery, and a concomitant midurethral sling) showed excellent performance for predicting bothersome stress urinary incontinence (area under the curve 0.74, 95% confidence interval 0.62–0.86) and outperformed the CUPIDO model (area under the curve 0.63, 95% confidence interval 0.49–0.76; DeLong's test P = 0.014). Conclusions: This prediction model might be a useful tool to guide patient decision making regarding a concomitant continence procedure at the time of prolapse surgery. The predictive value of this model needs to be validated further in cohorts with different characteristics. The proposed prediction model for bothersome stress urinary incontinence after prolapse surgery outperforms an existing model. The proposed prediction model for bothersome stress urinary incontinence after prolapse surgery outperforms an existing model. Linked article This article is commented on by J. Marinus van der Ploeg & Ewout W. Steyerberg, pp. 1165 in this issue. To view this minicommentary visit https://doi.org/10.1111/1471-0528.17067. [ABSTRACT FROM AUTHOR]

Singapora shinshana is a leafhopper native to mid‐Asia with a specific host range and is one of the least studied species within the genus. Recently, the species has been found to cause significant damage to host plants including ornamental trees, normally inflicted by its sucking behavior. This study uncovered more details on host and season preference of S. shinshana, damage potential and symptoms caused by its feeding behavior on ornamental trees in Korea, in addition to other records of other leafhoppers of economic importance. During the sticky trap survey period from 2017 to 2019, 12 leafhopper species were recovered from the eight selected ornamental tree species. Singapora shinshana was the most dominant species, constituting 94.8% of the total collected leafhopper population; with its highest incidence observed on Prunus serrulata, followed by Elaeagnus umbellata and Pseudocydonia sinensis. The high abundance on P. serrulata correlated with high damaged leaf percentages of 94.2%, 95.2%, and 98.1% in October 2017, 2018, and 2019, respectively. Interestingly, in terms of damaged leaf percentage, Rosa hybrida and Zelkova serrata were the second and third most damaged hosts despite the significantly lower population of the leafhopper on these trees. Furthermore, S. shinshana counts increased from late‐July to late‐September, with the peak evident during early August. Prunus serrulata can therefore be taken as one of the main host plants of S. shinshana. However, the potential of the host to suffer damage is not limited to population densities of the pest alone but also susceptibility and tolerance of the host plant. [ABSTRACT FROM AUTHOR]

Background: Potassium usnate (KU), a water-soluble form of usnic acid, shows anticancer activity. However, the underlying mechanisms have not been fully elucidated.Purpose: We aimed to identify the pathways involved in anticancer effects of KU in human gastric cancer (GC) and colorectal cancer (CRC) cells using RNA-sequencing (RNA-seq) based transcriptome analysis.Study Design: We analyzed the cytotoxic effects of KU to identify the common molecular events in GC and CRC cells upon KU exposure using unbiased approaches.Methods: Cell viability assays and western blot experiments were used to examine apoptotic changes, cell cycle arrest, and endoplasmic reticulum (ER) stress-induced cellular responses in KU-treated cells. Total RNA from KU-treated human GC and CRC cells was prepared for RNA-seq analysis. Gene ontology term and gene set enrichment analyses were used to identify the key mediators of the cytotoxic effects of KU. The expression of ER stress-induced apoptotic markers was evaluated using quantitative reverse-transcription PCR and western blot analysis. Chromatin immunoprecipitation assays for ATF3 and H3K27ac, and ATF3 knockdown were employed to verify the underlying molecular mechanisms. The inhibitory effect of KU on tumor growth in vivo was validated with metastatic tumor nodule formations in a mouse liver model.Results: KU exerted cytotoxicity in human GC and CRC cells through the activation of the ER stress-induced apoptotic pathway. KU stimulated ATF3 expression, an important mediator of molecular events of apoptosis. ATF3 binds to the promoter region of ATF3, CHOP, GADD34, GADD45A, DR5, and PUMA genes and subsequently promoted apoptotic events. Knockdown of ATF3 significantly reduced the expression of ATF3 target genes and the cytotoxic effects of KU. The intraperitoneal injection of KU induced ATF3 and the apoptosis of implanted colon cancer cells, resulting in reduced metastatic tumor growth in the mouse livers.Conclusion: KU exerts cytotoxic effects in human GC and CRC cells by triggering ER stress-induced apoptosis via an ATF3 dependent pathway. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is a heterogeneous disease that has complex causes and mechanisms of development. Currently, patient treatment options depend on the breast cancer molecular subtype, which is classified based on the presence or absence of hormone receptors and HER2. However, this classification system has limitations in terms of predicting responsiveness to anticancer drugs and patient outcomes. In this study, we present a new approach to classifying molecular breast cancer subtypes: it is based on changes in histone modifications in the promoter region of the MAGEA12 locus, which we found related closely to MAGEA12 expression and MAGEA12-associated malignancy of breast cancer cells. After decades-long efforts to diagnose and treat breast cancer, the management strategy that has proved most successful to date is molecular-subtype-specific inhibition of the hormone receptors and HER2 that are expressed by individual cancers. Melanoma-associated antigen (MAGE) proteins comprise >40 highly conserved members that contain the MAGE homology domain. They are often overexpressed in multiple cancers and contribute to cancer progression and metastasis. However, it remains unclear whether the biological activity arising from MAGE gene expression is associated with breast cancer subtypes. In this study, we analyzed the RNA-sequencing (RNA-seq) data of 70 breast cancer cell lines and found that MAGEA12 and MAGEA3 were highly expressed in a subset of these lines. Significantly, MAGEA12 and MAGEA3 expression levels were independent of hormone receptor expression levels but were closely associated with markers of active histone modifications. This indicates that overexpression of these genes is attributable to epigenetic deregulation. RNA-seq of MAGEA12-depleted cells was then used to identify 382 candidate targets of MAGEA12 that were downregulated by MAGEA12 depletion. Furthermore, our gain-of-function experiments showed that MAGEA12 overexpression promoted aggressive behaviors of malignant breast cancer cells, including enhancing their cell migration and invasion. These changes were associated with increased epigenetic deregulation of the MAGEA12 signature genes. Thus, MAGEA12 may play an important role in breast cancer malignancy. Taken together, our findings suggest that MAGEA12 could be a promising therapeutic target in breast cancer, and its overexpression and epigenetic changes could serve as subtype classification biomarkers. [ABSTRACT FROM AUTHOR]

Cancer metastasis is the primary cause of cancer-related death and metastatic cancer has circulating-tumor cells (CTCs), which circulate in the bloodstream before invading other organs. Thus, understanding the precise role of CTCs may provide new insights into the metastasis process and reduce cancer mortality. However, the molecular characteristics of CTCs are not well understood due to a lack of number of CTCs. Therefore, suspension cells were generated from MDA-MB-468 cells to mimic CTCs, and we investigate the microRNA (miRNA)-dependent molecular networks and their role in suspension cells. Here, we present an integrated analysis of mRNA and miRNA sequencing data for suspension cell lines, through comparison with adherent cells. Among the differentially regulated miRNA–mRNAs axes, we focus on the miR-146a-Neuropilin2 (NRP2) axis, which is known to influence tumor aggressiveness. We show that miR-146a directly regulates NRP2 expression and inhibits Semaphorin3C (SEMA3C) signaling. Functional studies reveal that miR-146a represses SEMA3C-induced invasion and proliferation by targeting NRP2. Finally, high-NRP2 is shown to be associated with poor outcomes in breast cancer patients. This study identifies the key role of the miR-146a–NRP2 signaling axis that is critical for the regulation of migration and invasion in CTC-mimicking cells. [ABSTRACT FROM AUTHOR]

The Pacific codGadus macrocephalusis a commercially important species belonging to the family Gadidae. In this study, we performed the first sequencing and assembly of the complete mitochondrial genome ofG. macrocephalus. The complete mitochondrial genome is 16,567 bp long, consisting of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and a control region. It has the typical vertebrate mitochondrial gene arrangement. Phylogenetic analysis using the mitochondrial genomes of 15 species showed thatG. macrocephalusclusters withG. ogac. This mitochondrial genome provides potentially important resources for performing population genetic analysis and addressing phylogenetic issues. [ABSTRACT FROM PUBLISHER]

The sole purpose of the mammary gland is the production of milk and during lactation more than 95% of the mRNA in secreting epithelial cells is contributed by less than 10 genes. Control relays regulating these genes are characterized by two astounding features, their ability to activate expression more than 10,000-fold during pregnancy and prevent regulatory spillover to neighboring genes. Studies in our laboratory focus on the critical roles of the common cytokine-inducible transcription factor (TF) STAT5 and the chromatin factor CTCF in the establishment of mammary-specific enhancers and the organization of regulatory chromatin domains that prevent regulatory spillover of these powerful enhancers to neighboring genetic loci. Through ChIP-seq experiments we defined the entirety of mammary enhancers in the mouse genome. These enhancers are characterized by the presence of H3K27ac and the joint binding of the TFs STAT5, GR, NFIB and MED1. CRISPR/CAS9 gene editing in mice was used to explore the role of defined STAT5 binding sites in the establishment and function of mammary-specific enhancers. Notably, STAT5 is the pioneer factor in the establishment and function of a subset of mammary enhancers. CTCF ChIP-seq experiments established putative chromatin boundaries of mammary-specific genetic islands. Using CRISPR/CAS9 CTCF sites within and surrounding mammary-specific islands were mutated in mice and their functional significance in establishing mammary-restricted gene regulation was investigated. [ABSTRACT FROM AUTHOR]

Background/aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression., Methods: Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD., Results: After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort., Conclusion: We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.

This review aimed to summarize the complications and surgical outcomes of robot-assisted sacrocolpopexy. Nineteen original articles on 1,440 robotic sacrocolpopexies were reviewed, and three systematic reviews and meta-analyses were summarized in terms of intraoperative, perioperative, postoperative, and/or surgical outcomes. Robotic sacrocolpopexy has demonstrated low overall complication rates and favorable surgical outcomes. Nevertheless, long-term follow-up outcomes regarding objective and/or subjective prolapse recurrence, reoperation rates, and mesh-related complications remain unclear. Further research is required to demonstrate whether the robotic approach for sacrocolpopexy is feasible or can become the modality of choice in the future when performing sacrocolpopexy.

Importance: Despite recognition of the critical role of the apex in vaginal support, there is no consensus on the anatomic criteria for clinically relevant apical prolapse., Objective: The aim of this study was to define an optimal anatomic criterion for clinically relevant apical prolapse., Study Design: This retrospective cohort study included 3,690 patients who had visited a tertiary hospital for ambulatory urogynecologic care. Vaginal bulge symptom was defined as a response of "somewhat," "moderately," or "quite a bit" to Question 3 on the Pelvic Floor Distress Inventory-20. Receiver operating characteristic curves were generated for a vaginal bulge symptom and apical support (Pelvic Organ Prolapse Quantification point C and C/total vaginal length [TVL])., Results: Both point C and the C-to-TVL ratio (C/TVL) had excellent performance for predicting vaginal bulge symptoms (area under the curve, 0.917 and 0.927, respectively). The optimal cutoffs were -3.0 for C and -0.50 for C/TVL. When we analyzed the data set according to the TVL, there was a significant difference in the cutoffs for C, whereas those for C/TVL had little difference. There was no difference in the cutoffs of C and C/TVL according to hysterectomy status., Conclusions: The C/TVL is more appropriate than point C as a measure to define an anatomic criterion for clinically relevant apical prolapse. Descent of the vaginal apex beyond the halfway point of the vagina could be considered as an anatomic threshold for clinically relevant apical prolapse. This finding needs to be validated in nonurogynecology populations., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Cancer stem-like cells (CSCs) have been suggested to be responsible for chemoresistance and tumor recurrence owing to their self-renewal capacity and differentiation potential. Although WEE1 is a strong candidate target for anticancer therapies, its role in ovarian CSCs is yet to be elucidated. Here, we show that WEE1 plays a key role in regulating CSC properties and tumor resistance to carboplatin via a microRNA-dependent mechanism. We found that WEE1 expression is upregulated in ovarian cancer spheroids because of the decreased expression of miR-424 and miR-503, which directly target WEE1. The overexpression of miR-424/503 suppressed CSC activity by inhibiting WEE1 expression, but this effect was reversed on the restoration of WEE1 expression. Furthermore, we demonstrated that NANOG modulates the miR-424/503-WEE1 axis that regulates the properties of CSCs. We also demonstrated the pharmacological restoration of the NANOG-miR-424/503-WEE1 axis and attenuation of ovarian CSC characteristics in response to atorvastatin treatment. Lastly, miR-424/503-mediated WEE1 inhibition re-sensitized chemoresistant ovarian cancer cells to carboplatin. Additionally, combined treatment with atorvastatin and carboplatin synergistically reduced tumor growth, chemoresistance, and peritoneal seeding in the intraperitoneal mouse models of ovarian cancer. We identified a novel NANOG-miR-424/503-WEE1 pathway for regulating ovarian CSCs, which has potential therapeutic utility in ovarian cancer treatment., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

The demand for uterine preservation in pelvic reconstructive surgery for uterovaginal prolapse is steadily increasing, and several procedures have been introduced, such as sacrospinous hysteropexy, uterosacral hysteropexy, sacrohysteropexy, and hysteropectopexy. However, the benefits and risks of uterine-preserving surgeries are not well understood. This review discusses the current evidence surrounding uterine-preserving surgery for uterovaginal prolapse repair. This may help surgeons and patients have a balanced discussion on how and on whom to perform uterine-preserving surgery.

Objective: To identify the factors associated with unsuccessful pessary fitting and reasons for pessary discontinuation in Korean women with pelvic organ prolapse (POP)., Methods: The medical records of 234 patients who underwent pessary fitting for the management of symptomatic POP were retrospectively reviewed. A ring pessary with or without support was used. Successful pessary fitting was defined as the ability to wear a pessary for 2 weeks without any discomfort. Factors associated with unsuccessful pessary fitting were determined using a multivariable logistic regression analysis. A Kaplan-Meier survival curve was obtained to examine the probability of continuing pessary use over the follow-up period. The reasons for the discontinuation of pessary were identified., Results: Two-hundred-and-twenty-five women were included in the analysis. The rate of unsuccessful pessary fitting was 40%. Prior hysterectomy (odds ratio [OR], 4.13; 95% confidence interval [CI], 1.81-9.42) and POP quantification stage III-IV (OR, 2.49; 95% CI, 1.28-4.85) were independent risk factors for unsuccessful pessary fitting. Among the patients with successful pessary fitting, the median time to discontinuation of pessary use was 4 years. The most common causes of discontinued use were vaginal erosion (45.3%) and urinary incontinence (26.5%)., Conclusion: Patients with a history of hysterectomy and advanced-stage POP are at risk for an unsuccessful fitting of the ring pessary. Vaginal erosion is the main reason for discontinued use among patients with successful pessary fitting.

One new species of the genus Alnetoidia Dlabola, A. (Alnetoidia) flava sp. nov. and a newly recorded species, A. (Alnetoidia) satsumana (Matsumura, 1932) are reported from the Korean Peninsula, and a key to the Korean species is provided.

Cancer cells utilize epigenetic alterations to acquire autonomous capabilities for tumor maintenance. Here, we show that pancreatic ductal adenocarcinoma (PDA) cells utilize super-enhancers (SEs) to activate the transcription factor EVI1 (ecotropic viral integration site 1) gene, resulting in activation of an EVI1-dependent transcription program conferring PDA tumorigenesis. Our data indicate that SE is the vital cis -acting element to maintain aberrant EVI1 transcription in PDA cells. Consistent with disease progression and inferior survival outcomes of PDA patients, we further show that EVI1 upregulation is a major cause of aggressive tumor phenotypes. Specifically, EVI1 promotes anchorage-independent growth and motility in vitro and enhances tumor propagation in vivo . Mechanistically, EVI1-dependent activation of tumor-promoting gene expression programs through the stepwise configuration of the active enhancer chromatin attributes to these phenotypes. In sum, our findings support the premise that EVI1 is a crucial driver of oncogenic transcription programs in PDA cells. Further, we emphasize the instructive role of epigenetic aberrancy in establishing PDA tumorigenesis., (© The Author(s) 2021. Published by Oxford University Press on behalf of NAR Cancer.)

Cancer metastasis is the primary cause of cancer-related death and metastatic cancer has circulating-tumor cells (CTCs), which circulate in the bloodstream before invading other organs. Thus, understanding the precise role of CTCs may provide new insights into the metastasis process and reduce cancer mortality. However, the molecular characteristics of CTCs are not well understood due to a lack of number of CTCs. Therefore, suspension cells were generated from MDA-MB-468 cells to mimic CTCs, and we investigate the microRNA (miRNA)-dependent molecular networks and their role in suspension cells. Here, we present an integrated analysis of mRNA and miRNA sequencing data for suspension cell lines, through comparison with adherent cells. Among the differentially regulated miRNA-mRNAs axes, we focus on the miR-146a-Neuropilin2 (NRP2) axis, which is known to influence tumor aggressiveness. We show that miR-146a directly regulates NRP2 expression and inhibits Semaphorin3C (SEMA3C) signaling. Functional studies reveal that miR-146a represses SEMA3C-induced invasion and proliferation by targeting NRP2. Finally, high-NRP2 is shown to be associated with poor outcomes in breast cancer patients. This study identifies the key role of the miR-146a-NRP2 signaling axis that is critical for the regulation of migration and invasion in CTC-mimicking cells.

Background: Polycystic kidney disease (PKD) involves renal cysts arising from proliferating tubular cells. Autophagy has been recently suggested as a potential therapeutic target in PKD, and mammalian target of rapamycin (mTOR) is a key negative regulator of autophagy. However, the effect of autophagy regulation on cystogenesis has not been elucidated in PKD mice., Methods: Clinical validation was performed using GEO datasets and autosomal dominant polycystic kidney disease (ADPKD) patient samples. Newly established PKD and LC3 transgenic mice were used for in vivo verifications, and additional tests were performed in vitro and in vivo using multiple autophagy drugs., Findings: Neither autophagy stimulation nor LC3 overexpression alleviated PKD. Furthermore, we observed the inhibitory effect of an autophagy inhibitor on cysts, indicating its possible therapeutic use in a specific group of patients with ADPKD., Interpretation: Our findings provide a novel insight into the pathogenesis related to autophagy in PKD, suggesting that drugs related to autophagy regulation should be considered with caution for treating PKD., Funding Sources: This work was supported by grants from the Bio & Medical Technology Development Program; the Collaborative Genome Program for Fostering New Post-Genome Industry of the NRF; the Basic Science Program., Competing Interests: Declaration of Competing Interest J.H. Park, G.T. Oh and J.Y. Ko have filed a patent in South Korea for the establishment of the Ift46-deleted model (patent number: 10-1618124). The others have nothing to disclose., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

One new leafhopper species, L. dangjinensis sp. nov. is described, and L. hebeiensis Cai, Liang Wang, 1992 is reported from Korea for the first time. Descriptions, photographs, illustrations and biological information of the new species are provided. A key to the Korean Limassolla species is also given. Limassolla macrobipunctata Hossain, Kwon, Suh Kwon, 2019 is synonymised with L. ishiharai Dworakowska, 1972.

Chronic liver disease progresses through several stages, fatty liver, steatohepatitis, cirrhosis, and eventually, it leads to hepatocellular carcinoma (HCC) over a long period of time. Since a large proportion of patients with HCC are accompanied by cirrhosis, it is considered to be an important factor in the diagnosis of liver cancer. This is because cirrhosis leads to an irreversible harmful effect, but the early stages of chronic liver disease could be reversed to a healthy state. Therefore, the discovery of biomarkers that could identify the early stages of chronic liver disease is important to prevent serious liver damage. Biomarker discovery at liver cancer and cirrhosis has enhanced the development of sequencing technology. Next generation sequencing (NGS) is one of the representative technical innovations in the biological field in the recent decades and it is the most important thing to design for research on what type of sequencing methods are suitable and how to handle the analysis steps for data integration. In this review, we comprehensively summarized NGS techniques for identifying genome, transcriptome, DNA methylome and 3D/4D chromatin structure, and introduced framework of processing data set and integrating multi-omics data for uncovering biomarkers. [BMB Reports 2020; 53(6): 299-310].

The primary cilium is a microtubule-based structure projecting from a cell. Although the primary cilium shows no motility, it can recognize environmental stimuli. Thus, ciliary defects cause severe abnormalities called ciliopathies. Ciliogenesis is a very complex process and involves a myriad of components and regulators. In order to excavate the novel positive regulators of ciliogenesis, we performed mRNA microarray using starved NIH/3T3 cells. We selected 62 murine genes with corresponding human orthologs, with significantly upregulated expression at 24 h after serum withdrawal. Finally, calpain-6 was selected as a positive regulator of ciliogenesis. We found that calpain-6 deficiency reduced the percentage of ciliated cells and impaired sonic hedgehog signaling. It has been speculated that this defect might be associated with decreased levels of α-tubulin acetylation at lysine 40. This is the first study to report a novel role of calpain-6 in the formation of primary cilia. [BMB Reports 2019; 52(10): 619-624].

Altered miRNA (miR) expression occurs in various diseases. However, the therapeutic effect of miRNAs in autosomal dominant polycystic kidney disease (ADPKD) is unclear. Genome-wide analyses of miRNA expression and DNA methylation status were conducted to identify crucial miRNAs in end-stage ADPKD. miR-192 and -194 levels were down-regulated with hypermethylation at these loci, mainly in the intermediate and late stages, not in the early stage, of cystogenesis, suggesting their potential impact on cyst expansion. Cyst expansion has been strongly associated with endothelial-mesenchymal transition (EMT). Zinc finger E-box-binding homeobox-2 and cadherin-2, which are involved in EMT, were directly regulated by miR-192 and -194. The therapeutic effect of miR-192 and -194 in vivo and in vitro were assessed. Restoring these miRs by injection of precursors influenced the reduced size of cysts in Pkd1 conditional knockout mice. miR-192 and -194 may act as potential therapeutic targets to control the expansion and progression of cysts in patients with ADPKD.-Kim, D. Y., Woo, Y. M., Lee, S., Oh, S., Shin, Y., Shin, J.-O., Park, E. Y., Ko, J. Y., Lee, E. J., Bok, J., Yoo, K. H., Park, J. H. Impact of miR-192 and miR-194 on cyst enlargement through EMT in autosomal dominant polycystic kidney disease.

The manila clam, Ruditapes philippinarum, is an important bivalve species in worldwide aquaculture including Korea. The aquaculture production of R. philippinarum is under threat from diverse environmental factors including viruses, microorganisms, parasites, and water conditions with subsequently declining production. In spite of its importance as a marine resource, the reference genome of R. philippinarum for comprehensive genetic studies is largely unexplored. Here, we report the de novo whole-genome and transcriptome assembly of R. philippinarum across three different tissues (foot, gill, and adductor muscle), and provide the basic data for advanced studies in selective breeding and disease control in order to obtain successful aquaculture systems. An approximately 2.56 Gb high quality whole-genome was assembled with various library construction methods. A total of 108,034 protein coding gene models were predicted and repetitive elements including simple sequence repeats and noncoding RNAs were identified to further understanding of the genetic background of R. philippinarum for genomics-assisted breeding. Comparative analysis with the bivalve marine invertebrates uncover that the gene family related to complement C1q was enriched. Furthermore, we performed transcriptome analysis with three different tissues in order to support genome annotation and then identified 41,275 transcripts which were annotated. The R. philippinarum genome resource will markedly advance a wide range of potential genetic studies, a reference genome for comparative analysis of bivalve species and unraveling mechanisms of biological processes in molluscs. We believe that the R. philippinarum genome will serve as an initial platform for breeding better-quality clams using a genomic approach., (© The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)