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Abstract Background The accuracy of intraoral scanning is critical for computer-aided design/computer-aided manufacturing workflows in dentistry. However, data regarding the scanning accuracy of various adjacent restorative materials and intraoral scanners are lacking. This in vitro study aimed to evaluate the effect of adjacent restorative material type and CEREC's intraoral scanners on the accuracy of intraoral digital impressions for inlay cavities. Methods The artificial tooth was prepared with an occlusal cavity depth of 2 mm, a proximal box width at the gingival floor of 1.5 mm, and an equi-gingival margin extended disto-occlusally at the transition line angle on both the lingual and buccal sides for an inlay restoration. The adjacent teeth were veneered with crowns made of gold and zirconia, and an artificial tooth (resin) was utilized as the control group. The inlay cavity and adjacent teeth (Gold, Zirconia, and resin) were scanned 10 times using Chairside Economical Restoration of Esthetic Ceramics (CEREC) Primescan (PS), Omnicam (OC), and Bluecam (BC). A reference scan was obtained using a laboratory scanner (3-shape E3). Scanning was performed according to the manufacturer's instructions, including powder application for the BC group. Standard tesselation language files were analyzed using a three-dimensional analysis software program. Experimental data were analyzed using a two-way analysis of variance and the Tukey’s post-hoc comparison test. Results The restorative materials of the adjacent teeth significantly affected the accuracy of the intraoral digital impressions (p PS > OC. The average deviation in precision increased in the following order: PS>OC>BC (p

Abstract Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/β-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/β-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.

Abstract Identifying environmental effects on the reproduction cycle and sex hormones is essential for ensuring the sustainable productivity of Pacific bluefin tuna (PBT, Thunnus orientalis) aquaculture. In the present study, 70 PBTs, commercially farmed in sea cages near Yokjido Island, South Korea, were investigated from April 2020 to March 2021. Environmental data, including water temperature and photoperiod duration, were collected. The gonadosomatic index (GSI) was calculated, and male and female maturity stages were classified monthly in proportions based on histological analysis of the gonads. Male and female gonadal developmental stages were classified into four major stages. Mature male and female PBTs were observed from May to August and June to August, respectively. Monthly changes in sex steroid hormone levels in PBT plasma were evaluated. The GSI and sex steroid hormones of males and females increased in May, peaked in June, and decreased thereafter. Our results confirmed the reproductive potential of farmed PBT and verified that reproductive maturity is reached in July. This study, to the best of our knowledge, is the first to investigate the reproductive biology of PBT in South Korea, and our results constitute a reference for future research on PBT aquaculture.

Collagen is considered to be an intercellular adhesive that prevents tissue stretching or damage. It is widely utilized in cosmetic skin solutions, drug delivery, vitreous substitutions, 3D cell cultures, and surgery. In this study, we report the development of a green technology for manufacturing collagen peptides from flatfish skin using ultrasound and enzymatic treatment and a subsequent assessment on skin functionality. First, flatfish skin was extracted using ultrasound in distilled water (DW) for 6 h at 80 °C. Molecular weight analysis via high-performance liquid chromatography (HPLC) after treatment with industrial enzymes (alcalase, papain, protamex, and flavourzyme) showed that the smallest molecular weight (3.56 kDa) was achieved by adding papain (0.5% for 2 h). To determine functionality based on peptide molecular weight, two fractions of 1100 Da and 468 Da were obtained through separation using Sephadex™ G-10. We evaluated the effects of these peptides on protection against oxidative stress in human keratinocytes (HaCaT) cells, inhibition of MMP-1 expression in human dermal fibroblast (HDF) cells, reduction in melanin content, and the inhibition of tyrosinase enzyme activity in murine melanoma (B16F10) cells. These results demonstrate that the isolated low-molecular-weight peptides exhibit superior skin anti-oxidant, anti-wrinkle, and whitening properties.

Path planning for mobile robots poses a challenging optimization problem, requiring the discovery of a near-optimal path within diverse constraints. Conventional particle swarm optimization (PSO) algorithms encounter limitations in solving constrained problems, vulnerability to local optima, and premature convergence. To address these challenges, this paper proposes a bi-population PSO algorithm with a random perturbation strategy (BPPSO), which divides particles into two subpopulations. The first subpopulation enhances global search capabilities by considering the quality of particles and the optimal solution of a randomly selected particle when updating velocities. The second subpopulation strengthens local search using a linear cognitive coefficient adjustment strategy. Moreover, a counter tracks iteration without improvement in the global best position. Upon reaching a predefined threshold, random perturbation is added to the positions of all particles in both subpopulations, increasing diversity and enhancing the ability to escape local optima. The performance of BPPSO was experimentally validated across three benchmark functions and four environment models. The results have demonstrated that the proposed BPPSO outperforms existing PSO algorithms and other established path planning algorithms in terms of path quality and running time, highlighting the feasibility of BPPSO in resolving the challenge of mobile robot path planning.

Resin-based composite materials are commonly used for restorations, but their dimensional changes during the polymerization could cause various clinical problems. This study evaluated the influence of a base of different materials and thicknesses on the stress magnitude and distribution in a second maxillary premolar with an MOD resin composite restoration using three-dimensional finite element analysis. A sound tooth without cavity was considered as the control group (ST), and another group was restored with composite resin without applying a base material in a MOD cavity (CR). The other three groups were restored with composite resin along with the following base materials: glass ionomer cement, low-viscosity resin, and tricalcium silicate, respectively (CR-GIC, CR-LR, and CR-TS). These three groups were further divided into two subgroups according to the thickness of the base layer: thin (0.5 mm) and thick (1.0 mm). The stress distribution was compared using the maximum principal stress after polymerization shrinkage and vertical loading with 600 N on the occlusal surface. Group ST showed the lowest stress value, and its stress propagation was confined to outer enamel surfaces only. Group CR demonstrated the highest stress distribution in the tooth-restoration interface with increased failure risk on marginal areas. The thin and thick subgroups of the three groups with a base layer had lower stress levels than Group CR. The base materials reduced the marginal stress caused by polymerization shrinkage of composite resin in MOD cavities. Different base materials and thicknesses did not affect the stress distribution.

ObjectivesFertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST.Methods/materialsThis ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI ResultsAmong 251 eligible patients, Groups 1-4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4).ConclusionsIn low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction.

The aim of the present study is to provide a methodical platform for the development of lead compounds against cholangiocarcinoma. Coptisine was selected as a potential anti-cancer nominee from a pool of phytochemicals using an in silico 3-D docking screening technique and validated the anti-cancer effects against cholangiocarcinoma through the blockade of EGFR signaling depending on the cellular degradation. We also verified that coptisine had no cytotoxicity in different human normal cells when compared with the clinically approved anti-cancer drug, erlotinib. In vitro and in silico analyses revealed that coptisine can suppress the expression of various oncogenic molecules and administrating coptisine showed an anti-cholangiocarcinoma tumor growth or recurrence using in vivo models. Collectively, we propose that a well-organized methodical 3-D docking screening platform is an innovative technique for the discovery of anti-cancer drugs against malignant tumors, and coptisine might be a safe and effective anti-cancer reagent against cholangiocarcinoma.

Abstract Background The accuracy of intraoral scanning plays a crucial role in the workflow of computer-assisted design/computer-assisted manufacturing. However, data regarding scanning accuracy for inlay preparation designs are lacking. The purpose of this in vitro study was to evaluate the influence of the depth of the occlusal cavity and width of the gingival floor of the proximal box on the trueness and precision of intraoral scans for inlay restoration. Methods Artificial teeth were used in this study. Four types of preparations for mesio-occlusal inlay were performed on each #36 artificial tooth depending on two different depths of the occlusal cavity (1 mm and 2 mm) and widths of the gingival floor of the proximal box (1.5 mm and 2.5 mm). Artificial teeth were scanned 10 times each with Cerec Primescan AC, and another scan was performed subsequently with a laboratory scanner as a reference (n = 10). Standard tessellation language files were analyzed using a three-dimensional analysis software program. Experimental data were analyzed using two-way analysis of variance and the Bonferroni multiple comparison test. Results The narrow shallow group had significantly higher deviation values for trueness than the wide deep group (p 0.05). For the mean maximum positive deviation, the wide groups had significantly lower values than the narrow groups (p

Abstract Cisplatin resistance along with chemotherapy-induced neuropathic pain is an important cause of treatment failure for many cancer types and represents an unmet clinical need. Therefore, future studies should provide evidence regarding the mechanisms of potential targets that can overcome the resistance as well as alleviate pain. Here, we show that the emergence of cisplatin resistance is highly associated with EGFR hyperactivation, and that EGFR hyperactivation is arisen by a transcriptional increase in the pain-generating channel, TRPV1, via NANOG. Furthermore, TRPV1 promotes autophagy-mediated EGF secretion via Ca2+ influx, which activates the EGFR-AKT signaling and, consequentially, the acquisition of cisplatin resistance. Importantly, TRPV1 inhibition renders tumors susceptible to cisplatin. Thus, our findings indicate a link among cisplatin resistance, EGFR hyperactivation, and TRPV1-mediated autophagic secretion, and implicate that TRPV1 could be a crucial drug target that could not only overcome cisplatin resistance but also alleviate pain in NANOG+ cisplatin-resistant cancer.

Abstract Introduction This study aimed to verify the association between ovarian cancer (OC) and reproductive‐ and lifestyle‐related risk factors stratified by the subtype of OC. Methods In this matched case–control study derived from the Korean epithelial ovarian cancer study (Ko‐EVE), we calculated the risk of OC subtypes using odds ratios (ORs) and 95% confidence intervals (95% CIs) in a logistic regression model. Results As a result of matching, 531 cases and 2,124 controls were selected. Smoking had positive association with high‐grade serous (HGS) OC (OR = 2.69, 95% CI = 1.15–6.30), whereas alcohol consumption had positive association with mucinous type (MUC) (OR = 3.63, 95% CI = 1.39–9.49). Obesity (≥30 kg/m2) was associated with clear cell type (CLC) (OR = 4.57, 95% CI = 1.06–19.77). Spontaneous abortion was negatively associated with CLC (OR = 0.34, 95% CI = 0.13–0.90), in contrast to HGS (OR = 1.43, 95% CI = 0.96–2.15). Tubal ligation, hysterectomy, and oophorectomy were associated with decreased risk of HGS (OR = 0.14, 95% CI = 0.05–0.39; OR = 0.23, 95% CI = 0.07–0.73; OR = 0.28, 95% CI = 0.08–0.97, respectively). Early menarche was strongly associated with increased risk of CLC, but not MUC (OR = 6.11, 95% CI = 1.53–24.42; OR = 3.23, 95% CI = 0.98–10.86). Further, childbirth (≥2 times) was negatively associated with endometrioid type OC and CLC (OR = 0.11, 95% CI = 0.04–0.35; OR = 0.12, 95% CI = 0.02–0.37, respectively). Oral contraceptives and hormone replacement therapy were negatively associated with OC (OR = 0.61, 95% CI = 0.40–0.93; OR = 0.51, 95% CI = 0.32–0.80, respectively), and similar negative associations were also observed in HGS (OR = 0.69; OR = 0.60, respectively). Associations between family history of breast cancer and OC, regular exercise (≥5/week), and artificial abortion and OC were similar across all subtypes (OR = 3.92; OR = 0.41; OR = 0.72, respectively). Conclusion A heterogeneous association between some risk factors and the incidence of each subtype of epithelial OC was observed, suggesting that the carcinogenic mechanisms of each subtype may be partly different.

Summary: Stress granules (SGs) constitute a signaling hub that plays a critical role in type I interferon responses. Here, we report that growth arrest and DNA damage-inducible beta (Gadd45β) act as a positive regulator of SG-mediated interferon signaling by targeting G3BP upon RNA virus infection. Gadd45β deficiency markedly impairs SG formation and SG-mediated activation of interferon signaling in vitro. Gadd45β knockout mice are highly susceptible to RNA virus infection, and their ability to produce interferon and cytokines is severely impaired. Specifically, Gadd45β interacts with the RNA-binding domain of G3BP, leading to conformational expansion of G3BP1 via dissolution of its autoinhibitory electrostatic intramolecular interaction. The acidic loop 1- and RNA-binding properties of Gadd45β markedly increase the conformational expansion and RNA-binding affinity of the G3BP1-Gadd45β complex, thereby promoting assembly of SGs. These findings suggest a role for Gadd45β as a component and critical regulator of G3BP1-mediated SG formation, which facilitates RLR-mediated interferon signaling.

Abstract Background Cudrania tricuspidata is a perennial plant, and Sargassum fusiforme is a brown seaweed with numerous potential benefits, including anticancer, anti-inflammatory, and antioxidant activities. However, the efficacies of C. tricuspidata and S. fusiforme on hair growth have not yet been elucidated. Therefore, the present study examined the effects of C. tricuspidata and S. fusiforme extracts on hair growth in C57BL/6 mice. Results ImageJ demonstrated that drinking and skin application of C. tricuspidata and/or S. fusiforme extracts significantly increased the hair growth rate in the dorsal skin of C57BL/6 mice compared to the control group. Histological analysis confirmed that drinking and skin application of C. tricuspidata and/or S. fusiforme extracts for 21 days significantly increased the length of hair follicles on the dorsal skin of treated C57BL/6 mice compared to that in the control mice. RNA sequencing analysis revealed that hair growth cycle-related factors (anagen factors) such as Catenin Beta 1 (Ctnnb1) and platelet-derived growth factor (Pdgf) were upregulated (> twofold) only by C. tricuspidate extracts, whereas vascular endothelial growth factor (Vegf) and Wnts were upregulated by both C. tricuspidata or S. fusiforme applications in treated mice (compared to the control mice). In addition, oncostatin M (Osm, a catagen-telogen factor) was downregulated (

A service subgraph helps Internet-of-Things devices access resources in a dynamic Internet-of-Things device network. We propose a service subgraph generation method for Internet-of-Things device networks. Service subgraph generation aims to find more capable neighboring Internet-of-Things devices for service provisioning. We apply a line graph structure for an adequate representation of device resources. The line graph structure effectively represents the resources in the generated service subgraph. A general node classification problem constituting the generated service subgraph identifies the appropriate resource binding for service provisioning. A node in the service subgraph corresponds to a unique relationship between devices. Service provisioning is guaranteed by reinforcement learning based on the resource binding identified by node classification. The proposed line graph structure and resource binding significantly enhance the traditional intelligent resource allocation method. In addition, the proposed scheme can effectively attain service subgraphs with very low computational complexity. The proposed generative service provisioning generally has a significantly lower occupation probability than the swarm intelligence-based algorithm. The average value of the occupation probability is 0.49 with the proposed method. It is 0.12 lower than that of swarm intelligence-based algorithm.

Avian influenza virus (AIV) is a pathogen with zoonotic and pandemic potential. Migratory birds are natural reservoirs of all known subtypes of AIVs, except for H17N10 and H18N11, and they have been implicated in previous highly pathogenic avian influenza outbreaks worldwide. This study identified and characterized the first isolate of the H13N6 subtype from a Vega gull (Larus vegae mongolicus) in South Korea. The amino acid sequence of hemagglutinin gene showed a low pathogenic AIV subtype and various amino acid substitutions were found in the sequence compared to the reference sequence and known H13 isolates. High sequence homology with other H13N6 isolates was found in HA, NA, PB1, and PA genes, but not for PB2, NP, M, and NS genes. Interestingly, various point amino acid mutations were found on all gene segments, and some are linked to an increased binding to human-type receptors, resistance to antivirals, and virulence. Evolutionary and phylogenetic analyses showed that all gene segments are gull-adapted, with a phylogeographic origin of mostly Eurasian, except for PB2, PA, and M. Findings from this study support the evidence that reassortment of AIVs continuously occurs in nature, and migratory birds are vital in the intercontinental spread of avian influenza viruses.

The purpose of this study was to investigate the initiation of autophagy activation and apoptosis in nucleus pulposus cells under temporary compression (TC) and sustained compression (SC) to identify ideal research approaches in intervertebral disc degeneration. Various techniques were used: radiography (X-ray), magnetic resonance imaging (MRI), transmission electron microscope (TEM), H&E staining, Masson’s trichrome staining, immunohistochemistry (IHC) (LC3, beclin-1, and cleaved caspase-3), and real-time polymerase chain reaction (RT-qPCR) for autophagy-related (beclin-1, LC3, and P62) and apoptosis-related (caspase-3 and PARP) gene expression analysis. X-ray and MRI revealed varying degrees of disc degeneration, ranging from moderate to severe in both groups. The severity was directly linked to compression duration, with SC resulting in notably severe central NP cell degeneration. Surprisingly, TC also caused similar, though less severe, degeneration. Elevated expression of LC3 and beclin-1 was identified after 6 weeks, but it notably declined after 12 weeks. Central NP cells in both groups exhibited increased expression of cleaved caspase-3 that was positively correlated with the duration of SC. TC showed fewer apoptotic markers compared to SC. LC3, beclin-1, and P62 mRNA expression peaked after 6 weeks and declined after 12 weeks in both groups. Cleaved caspase-3 and PARP expression peaked in SC, positively correlating with longer compression duration, while TC showed lower levels of apoptosis gene expression. Furthermore, TEM results revealed different events of the autophagic degradation process after 2 weeks of compression. TCmay be ideal for studying early triggered autophagy-mediated degeneration, while SC may be ideal for studying late or slower-triggered apoptosis-mediated degeneration.

Background/objectiveHigh-grade serous ovarian carcinoma (HGSOC) is the most common histologic type of epithelial ovarian cancer (EOC). Due to its poor survival outcomes, it is essential to identify novel biomarkers and therapeutic targets. The hippo pathway is crucial in various cancers, including gynaecological cancers. Herein, we examined the expression of the key genes of the hippo pathway and their relationship with clinicopathological significance, immune cells infiltration and the prognosis of HGSOC.MethodsThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data were curated to analyse the mRNA expression as well as the clinicopathological association and correlation with immune cell infiltration in HGSOC. The protein levels of significant genes in the HGSOC tissue were analysed using Tissue Microarray (TMA)-based immunohistochemistry. Finally, DEGs pathway analysis was performed to find the signalling pathways associated with VGLL3.ResultsVGLL3 mRNA expression was significantly correlated with both advanced tumor stage and poor overall survival (OS) (p=0.046 and p=0.003, respectively). The result of IHC analysis also supported the association of VGLL3 protein with poor OS. Further, VGLL3 expression was significantly associated with tumor infiltrating macrophages. VGLL3 expression and macrophages infiltration were both found to be independent prognostic factors (p=0.003 and p=0.024, respectively) for HGSOC. VGLL3 was associated with four known and three novel cancer-related signalling pathways, thus implying that VGLL3 is involved in the deregulation of many genes and pathways.ConclusionOur study revealed that VGLL3 may play a distinct role in clinical outcomes and immune cell infiltration in patients with HGSOC and that it could potentially be a prognostic marker of EOC.

Undaria pinnatifida, a marine biological resource from which antioxidants such as polysaccharides can be obtained, is primarily distributed in the coastal areas of East Asia. Reactive oxygen species (ROS) are essential for physiological processes; however, excess ROS levels in the body result in cellular oxidative damage. Several extraction methods exist; however, factors such as long extraction times and high temperatures degrade polysaccharides. Therefore, this study aimed to increase the yield of U. pinnatifida sporophyll extract (UPE), a U. pinnatifida byproduct, using ultrasonication, an environmentally friendly extraction method, and identify UPE components with antioxidant activity. UPE_2, 4, 6, and 8 extracts were obtained at extraction times of 2, 4, 6, and 8 h, respectively. UPE_8 had the highest yield (31.91%) and polysaccharide (69.22%), polyphenol, (8.59 GAE μg/mg), and fucoxanthin contents (2.3 μg/g). UPE_8 showed the greatest protective and inhibitory effects on ROS generation in H2O2-damaged Vero cells. Ethanol precipitation of UPE_8 confirmed that UPE_8P (precipitate) had superior antioxidant activity in Vero cells compared to UPE_8S (supernatant). UPE_8P contained a large amount of polysaccharides, a major contributor to the antioxidant activity of UPE_8. This study shows that UPE_8 obtained using ultrasonication can be a functional food ingredient with excellent antioxidant activity.

Apoptosis has historically been considered the primary form of programmed cell death (PCD) and is responsible for regulating cellular processes during development, homeostasis, and disease. Conversely, necrosis was considered uncontrolled and unregulated. However, recent evidence has unveiled the significance of necroptosis, a regulated form of necrosis, as an important mechanism of PCD alongside apoptosis. The activation of necroptosis leads to cellular membrane disruption, inflammation, and vascularization. This process is crucial in various pathological conditions, including intervertebral disc degeneration (IVDD), neurodegeneration, inflammatory diseases, multiple cancers, and kidney injury. In recent years, extensive research efforts have shed light on the molecular regulation of the necroptotic pathway. Various stimuli trigger necroptosis, and its regulation involves the activation of specific proteins such as receptor-interacting protein kinase 1 (RIPK1), RIPK3, and the mixed lineage kinase domain-like (MLKL) pseudokinase. Understanding the intricate mechanisms governing necroptosis holds great promise for developing novel therapeutic interventions targeting necroptosis-associated IVDD. The objective of this review is to contribute to the growing body of scientific knowledge in this area by providing a comprehensive overview of necroptosis and its association with IVDD. Ultimately, these understandings will allow the development of innovative drugs that can modulate the necroptotic pathway, offering new therapeutic avenues for individuals suffering from necroptosis.

Abstract Cancer immunoediting drives the adaptation of tumor cells to host immune surveillance. Previously, we have demonstrated that immunoediting driven by cytotoxic T lymphocytes (CTLs) enriches NANOG+ tumor cells with immune-refractory properties. Here, we found that CTL-mediated immune pressure triggered cross-resistance of tumor cells to the complement system, a part of the innate immune system. In this process, NANOG upregulated the membrane-bound complement regulatory protein (mCRP) CD59 through promoter occupancy, thereby contributing to the resistance of tumor cells against complement-dependent cytotoxicity (CDC). Notably, targeting of NANOG sensitized the immune-refractory tumor cells to trastuzumab-mediated CDC. Collectively, our results revealed a possible mechanism through which selection imposed by T-cell based immunotherapy triggered complement-resistant phenotypes in the tumor microenvironment (TME), by establishing a firm molecular link between NANOG and CD59 in immune-edited tumor cells. We believe these results hold important implications for the clinical application of CDC-mediated therapeutic antibody.

Measurement(s) Microbiome Technology Type(s) Metagenome • Bacterial 16 S RNA Factor Type(s) Ageing • Co-housing • Parabiosis • Serum-injection • Akkermansia (AK) treatment Sample Characteristic - Organism Mus musculus Sample Characteristic - Environment animal cage Sample Characteristic - Location South Korea

Hormones may be key factors driving cancer development, and epidemiological findings suggest that steroid hormones play a crucial role in ovarian tumorigenesis. We demonstrated that high glucocorticoid receptor (GR) expression is associated with a poor prognosis of epithelial ovarian cancer. Recent studies have shown that the GR affects β-arrestin expression, and vice versa. Hence, we assessed the clinical significance of β-arrestin expression in ovarian cancer and determined whether β-arrestin and the GR synergistically have clinical significance and value as prognostic factors. We evaluated the expression of β-arrestins 1 and 2 and the GR in 169 patients with primary epithelial ovarian cancer using immunohistochemistry. The staining intensity was graded on a scale of 0–4 and multiplied by the percentage of positive cells. We divided the samples into two categories based on the expression levels. β-arrestin 1 and GR expression showed a moderate correlation, whereas β-arrestin 2 and GR expression did not demonstrate any correlation. Patients with high β-arrestin 1 and 2 expression exhibited improved survival rates, whereas patients with low GR expression showed a better survival rate. Patients with high β-arrestin 1 and low GR levels had the best prognosis among all groups. β-arrestin is highly expressed in ovarian cancer, suggesting its potential as a diagnostic and therapeutic biomarker. The combination of β-arrestin and GR demonstrated greater predictive prognostic power than GR expression alone, implicating another possible role in prognostication.

Although the mitochondrial genomes of most Acanthuriformes fish have been sequenced, this has not been done for Prionurinae fish yet. The Scalpel sawtail (Prionurus scalprum Valenciennes, 1835) found in all tropical and sub-tropical seas, is an important link between primary producers and higher trophic levels. In this study, the complete mitochondrial genome of the Scalpel sawtail, Prionurus scalprum Valenciennes, 1835 (accession number: OK323243) was sequenced. The complete mitochondrial genome included 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and a control region; the total length was 16,522 bp. The nucleotide composition of the genome was as follows: A, 28.46%; T, 27.62%; G, 16.46%; and C, 27.46%. All genes were encoded on the H-strand, except for the eight tRNA genes and NADH dehydrogenase subunit (ND6). A phylogenetic tree was constructed using the neighbor-joining (NJ) method and the phylogenetic position of the Scalpel sawtail was established. This provides useful data for future research on Acanthuridae fish.

Abstract Preterm birth affects approximately 5% to 7% of live births worldwide and is the leading cause of neonatal morbidity and mortality. Amniotic fluid supernatant (AFS) contains abundant cell-free nucleic acids (cfNAs) that can provide genetic information associated with pregnancy complications. In the current study, cfNAs of AFS in the early second-trimester before the onset of symptoms of preterm birth were analyzed, and we compared gene expression levels between spontaneous preterm birth (n = 5) and term birth (n = 5) groups using sequencing analysis. Differential expression analyses detected 24 genes with increased and 6 genes with decreased expression in the preterm birth group compared to term birth. Upregulated expressions of RDH14, ZNF572, VOPP1, SERPINA12, and TCF15 were validated in an extended AFS sample by quantitative PCR (preterm birth group, n = 21; term birth group, n = 40). Five candidate genes displayed a significant increase in mRNA expression in immortalized trophoblast HTR-8/SVneo cell with H2O2 treatment. Moreover, the expression of five candidate genes was increased to more than twofold by pretreatment with lipopolysaccharide in HTR-8/SVneo cells. Changes in gene expression between preterm birth and term birth is strongly correlated with oxidative stress and infection during pregnancy. Specific expression patterns of genes could be used as potential markers for the early identification of women at risk of having a spontaneous preterm birth.

Abstract Background The gut microbiota is associated with diverse age-related disorders. Several rejuvenation methods, such as probiotic administration and faecal microbiota transplantation, have been applied to alter the gut microbiome and promote healthy ageing. Nevertheless, prolongation of the health span of aged mice by remodelling the gut microbiome remains challenging. Results Here, we report the changes in gut microbial communities and their functions in mouse models during ageing and three rejuvenation procedures including co-housing, serum-injection and parabiosis. Our results showed that the compositional structure and gene abundance of the intestinal microbiota changed dynamically during the ageing process. Through the three rejuvenation procedures, we observed that the microbial community and intestinal immunity of aged mice were comparable to those of young mice. The results of metagenomic data analysis underscore the importance of the high abundance of Akkermansia and the butyrate biosynthesis pathway in the rejuvenated mouse group. Furthermore, oral administration of Akkermansia sufficiently ameliorated the senescence-related phenotype in the intestinal systems in aged mice and extended the health span, as evidenced by the frailty index and restoration of muscle atrophy. Conclusions In conclusion, the changes in key microbial communities and their functions during ageing and three rejuvenation procedures, and the increase in the healthy lifespan of aged mice by oral administration of Akkermansia. Our results provide a rationale for developing therapeutic strategies to achieve healthy active ageing. Video abstract

The adhesion molecule Nectin-4 is a new potential therapeutic target for different types of cancer; however, little is known about its diagnosis significance in endometrial cancer (EC). We found that Nectin-4 expression was significantly higher in EC tissues than in nonadjacent normal tissue. The area under the receiver operating characteristic curve value of 0.922 indicated good diagnostic accuracy for Nectin-4 expression in EC. Furthermore, Nectin-4 expression was associated with DNA mismatch repair (MMR) protein deficiency. Notably, the high Nectin-4 expression group of patients with MSH2/6-deficient EC had shorter progression-free survival than that of the low Nectin-4 expression group. The number of lymphovascular space invasion-positive patients in groups with MMR deficiency and high Nectin-4 expression was also increased compared with that in the low Nectin-4 expression group. Bioinformatics analysis revealed that alteration in Nectin-4 and MMR genes is associated with Nectin-4 expression in EC. To the best of our knowledge, this is the first study to show that Nectin-4 expression may be a potential biomarker for EC diagnosis and that high Nectin-4 expression in MMR-deficient patients with EC can predict short progression-free survival, thus providing clues to identify patients for adjuvant therapy.

Ovarian clear cell carcinoma (OCCC) reportedly develops from endometriosis. However, the molecular mechanism underlying its malignant progression to OCCC remains elusive. This study aimed to identify an essential gene in the malignant transformation of endometriosis to OCCC. We performed RNA sequencing in formalin‐fixed, paraffin‐embedded (FFPE) tissues of endometriosis (n = 9), atypical endometriosis (AtyEm) (n = 18), adjacent endometriosis to OCCC (AdjEm) (n = 7), and OCCC (n = 17). We found that tetraspanin 1 (TSPAN1) mRNA level was significantly increased by 2.4‐ (DESeq2) and 3.4‐fold (edgeR) in AtyEm and by 80.7‐ (DESeq2) and 101‐fold (edgeR) in OCCC relative to endometriosis. We confirmed that TSPAN1 protein level was similarly overexpressed in OCCC tissues and cell lines. In immortalized endometriosis cell lines, TSPAN1 overexpression enhanced cell growth and invasion. Mechanistically, TSPAN1 triggered AMP‐activated protein kinase (AMPK) activity, promoting endometriosis and cell growth. Upregulated levels of TSPAN1 are considered an early event in the development of high‐risk endometriosis that could progress to ovarian cancer. Our study suggests the potential of TSPAN1 as a screening candidate for high‐risk endometriosis.

Abstract Background Epidural fibrosis is one of the aetiologies of pain following a spinal revision surgery. It is reported that the specific members of the mitogen – activated protein kinases (MAPK) family might mediate neuropathic pain. However, roles of epidural fibrosis caused by repeated spinal surgeries and pain-related proteins in causing the post spinal surgery syndrome remain unknown. Using a rat spinal surgery epidural fibrosis and adhesion model, in this study, we evaluated and investigated the relationship between pain markers and epidural fibrosis. Methods Sprague–Dawley rats that underwent the spinal surgery were divided into three groups: group A (single laminectomy), group B (two repeated surgeries) and group C (three repeated surgeries). Dural thickness was measured in each experimental group, and immunohistochemical analysis and western blotting of mitogen-activated protein kinases were performed (ERK, p38 and JNK) using the spine cord. Results Dural thickness was 6.363 ± 1.911 μm in group A, 13.238 ± 2.123 μm in group B and 19.4 ± 2.115 μm in group C, respectively. In the western blotting, phosphorylated ERK expression gradually increased with the number of repeated surgeries, and expression in groups B (1.77-fold) and C (2.42-fold) increased as compared to expression in group A. Phosphorylated p38 showed an increasing trend with the number of repeated surgeries, and groups B (1.17-fold) and C (1.33-fold) expression increased compared with group A. However, phosphorylated JNK expression did not gradually increase with the number of repeated surgeries, and groups B (1.62-fold) and C (1.43-fold) expression increased compared with group A. Excluding phosphorylated JNK, immunohistochemical analysis revealed that phosphorylated ERK and p38 expression gradually increased with the number of repeated surgeries in the spine dorsal horn, as evidenced by western blotting. Conclusions Repeated spinal surgeries may increase dural thickness and expression of phosphorylated ERK and p38 in the spinal dorsal horn, and it suggests that the neuropathic pain is likely induced by epidural fibrosis and that the pain increases with the number of repeated surgeries.

Selenium is a promising multi-target chemotherapeutic agent with controversial clinical results. Hence, reassessing the anticancer effects of Se is necessary to clearly understand the potential of high-dose selenium in cancer treatment. Here, we observed that high-dose sodium selenite (SS) significantly decreased the proliferation and increased the death of ovarian cancer cells, mediated by an increased generation of reactive oxygen species. Notably, high-dose SS decreased the levels of glutathione peroxidase (GPx), a selenoprotein with antioxidant properties, without altering other selenoproteins. Furthermore, high-dose SS triggered lipid peroxidation and ferroptosis, a type of iron-dependent cell death, due to dysregulated GPx4 pathways. We demonstrated that intravenous high-dose SS significantly reduced the tumor growth and weight in SKOV3-bearing mice. Consistent with our in vitro results, mice with SKOV3 cells treated with high-dose SS showed decreased GPx4 expression in tumors. Therefore, we highlight the significance of high-dose SS as a potential chemotherapeutic agent for ovarian cancer. High-dose SS-mediated ferroptotic therapy integrating glutathione depletion and ROS generation is a promising strategy for cancer therapy.

Nanog can confer resistance to cancer immunotherapy by promoting AKT activity. Here, the authors demonstrate that HSP90A is a Nanog target that stabilizes the AKT coactivator TCL1, thereby activating AKT, and that HSP90A inhibition can enhance the anti-tumor efficacy of adoptive T cell transfer and checkpoint blockade.

Abstract Background Transcription factors forkhead box protein O1 (FOXO1) and paired box 3 (PAX3) have been reported to play important roles in various cancers. However, their role in epithelial ovarian cancer (EOC) has not been elucidated yet. Therefore, we evaluated the expression and clinical significance of FOXO1 and PAX3 in EOC. Methods Immunohistochemical analyses of FOXO1 and PAX3 in 212 EOCs, 57 borderline ovarian tumors, 153 benign epithelial ovarian tumors, and 79 nonadjacent normal epithelial tissues were performed using tissue microarray. Various clinicopathological variables, including the survival of EOC patients, were compared. In addition, the effect of FOXO1 on cell growth was assessed in EOC cell lines. Results FOXO1 and PAX3 protein expression levels were significantly higher in EOC tissues than in nonadjacent normal epithelial tissues, benign tissues, and borderline tumors (all p

Abstract Background The recent advances in human disease network have provided insights into establishing the relationships between the genotypes and phenotypes of diseases. In spite of the great progress, it yet remains as only a map of topologies between diseases, but not being able to be a pragmatic diagnostic/prognostic tool in medicine. It can further evolve from a map to a translational tool if it equips with a function of scoring that measures the likelihoods of the association between diseases. Then, a physician, when practicing on a patient, can suggest several diseases that are highly likely to co-occur with a primary disease according to the scores. In this study, we propose a method of implementing ‘n-of-1 utility’ (n potential diseases of one patient) to human disease network—the translational disease network. Results We first construct a disease network by introducing the notion of walk in graph theory to protein-protein interaction network, and then provide a scoring algorithm quantifying the likelihoods of disease co-occurrence given a primary disease. Metabolic diseases, that are highly prevalent but have found only a few associations in previous studies, are chosen as entries of the network. Conclusions The proposed method substantially increased connectivity between metabolic diseases and provided scores of co-occurring diseases. The increase in connectivity turned the disease network info-richer. The result lifted the AUC of random guessing up to 0.72 and appeared to be concordant with the existing literatures on disease comorbidity.

This paper proposes a parameter identification method for a PEM electrolyzer electrical equivalent circuit for pulse electrolysis. Since general water electrolysis mainly uses DC currents, identifying equivalent circuit parameters using electrical characteristics mostly ignores the operation frequency and unnecessarily adheres to the secondary RC model. However, looking at the Nyquist plot of the PEM electrolyzer, it can be confirmed that identifying the operational frequency is necessary, and the secondary RC model correction is essential. Therefore, the proposed method confirms the necessity of reconstructing an electrical equivalent circuit with a primary RC model by analyzing the transient cell voltage using step current inputs and calculating an appropriate operating frequency by identifying the parameters of the reconstructed equivalent circuit. To verify the proposed parameter identification method, a simulation was constructed from the raw test data of a 400 W commercial PEM electrolyzer. In addition, the hydrogen production amount was compared to DC using a pulse electrolysis experiment at the operating frequency obtained by the proposed method.

Blockchain network architecture is a promising technology for constructing highly secure Internet of Things (IoT) networks. IoT networks typically comprise various sensors and actuators. Blockchain network technology can be applied to secure control robots in smart factories or reliable drone deliveries in smart cities. The wide spread of transactions and shared smart contracts across blockchain networks guarantees ultimate network security. A typical wired blockchain network maintains sufficient redundancy within a stable configuration. However, IoT blockchain networks exhibit unavoidable instability. The dynamic configuration changes caused by flexible node membership make it impossible to achieve the same level of redundancy as a stable network. A trustworthy transaction spreading method provides practical transaction sharing for dynamic IoT networks. We propose a Q-learning framework and a graph convergence network (GCN) to search for the proper spreading path of each transaction. The proposed Q-learning framework determines the next spreading hop using node features. The GCN determines the reliable area based on the Q-learning results. The discovered reliable area guides the proper spreading path of transactions to the destination node. In addition, the proposed trustworthy transaction spreading was implemented over an InterPlanetary File system (IPFS). The IPFS-powered experiments confirmed the practicability of the proposed transaction spreading mechanism.

Aspect-based sentiment analysis is a text analysis technique that categorizes data by aspect and identifies the sentiment attributed to each one and a task for a fine-grained sentiment analysis. In order to accurately perform a fine-grained sentiment analysis, a sentiment word within a text, a target it modifies, and a holder who represents the sentiment word are required; however, they should be extracted in sequence because the sentiment word is an important clue for extracting the target, which is key evidence of the holder. Namely, the three types of information sequentially become an important clue. Therefore, in this paper, we propose a stepwise multi-task learning model for holder extraction with RoBERTa and Bi-LSTM. The tasks are sentiment word extraction, target extraction, and holder extraction. The proposed model was trained and evaluated under Laptop and Restaurant datasets in SemEval 2014 through 2016. We have observed that the performance of the proposed model was improved by using stepwised features that are the output of the previous task. Furthermore, the generalization effect has been observed by making the final output format of the model a BIO tagging scheme. This can avoid overfitting to a specific domain of the review text by outputting BIO tags instead of the words.

Autoimmune uveitis is an ocular inflammatory disease that is associated with genetic factors. Interleukin 10 (IL-10) is an immune-regulatory cytokine of autoimmune diseases. IL-10 is considered a candidate gene for uveitis. We evaluate the association of IL-10 with susceptibility to autoimmune uveitis. The results from seven studies were pooled in the meta-analysis, covering a total of 2893 cases of uveitis and 4873 controls. Published literature from MEDLINE and Embase was retrieved. Meta-analyses were conducted on the associations between autoimmune uveitis and the -1082 A/G and -819 C/T polymorphisms of the IL-10 gene. The meta-analysis revealed no association between uveitis and the IL-10 -1082 A allele (OR = 0.91, 95% CI = 0.64-1.30, p = 0.62). The recessive, dominant, and homozygous models of the IL-10 -1082 A/G allele also suggested no association between autoimmune uveitis and each genotype. The meta-analysis revealed significant association between uveitis and the -892 C allele (OR = 0.81, 95% CI = 0.67-0.98, p = 0.03). In addition, significant association was found in homozygous models (OR = 0.58, 95% CI = 0.36-0.92, p = 0.02). However, the dominant and recessive models of the IL-10 -819 C/T polymorphisms showed no association between uveitis and each genotype. This meta-analysis showed that the -1082 A/G polymorphisms of IL-10 were not associated with autoimmune uveitis, but the -819 C/T polymorphisms were significantly associated with uveitis.

Abstract The insufficient wireless frequency bands are likely to arise with the increase in mobile traffic demand. Many mobile operators suffer from a high annual increase in the cost of licensed wireless bands. Unlicensed bands present a potential opportunity for mobile operators. A single 5-GHz band with a large bandwidth provides faster transmission for each user. However, interference caused by existing wireless transmissions, such as Wi-Fi in unlicensed bands, is a serious issue in the effective utilization of unlicensed bands by mobile operators. The Listen-Before-Talk (LBT) was proposed as a promising method to ensure the coexistence of Wi-Fi and commercial mobile services such as LTE. We focus on effective control of the contention window (CW) size to maximize the operability of LBT. Control of the CW size depends on the repetition of extended clear channel assessment (ECCA). We introduce a dual threshold system that counts the repetition of ECCA. The newly developed NS-3-based unlicensed band network simulator shows the effectiveness of the proposed control mechanism. The results indicated that the advantage of the proposed method improves 4.3–7.6% than traditional LBT method. We develop a composite metric of throughput and fairness to evaluate the performance of LTE-LAA access.

As the demand for mobile traffic is growing, radio frequency bandwidths often become insufficient for guaranteeing specific performance. Utilizing unlicensed 5 GHz broadband bandwidths, the LWA system enables the synergistic use of LTE and WiFi systems based on link aggregation techniques, without critical deterioration of service quality. This provides considerable benefits to the mobile operators when they successfully operate two networks and maintain an optimal balance in managing network resources. This study addresses balancing and fairness for newly emerging LWA systems. In particular, we develop a two-stage LWA access framework based on the Nash bargaining game. The framework further improves fairness and efficiency in the LTE-WiFi resource utilization by incorporating user segmentations on the basis of user characteristics, such as service contract and usage patterns. Extensive experiments using a network simulator with an NS-3 unlicensed band produce good performance in terms of fairness and efficiency. The proposed scheme demonstrates better outcomes compared to the existing methods while concurrently using radio resources in the LWA system in a fair manner. Moreover, our approach presents a simple and fast decision-making process and requires simple user profiles-contract status and traffic generation history. Therefore, the proposed scheme is far lighter and more flexible than traditional approaches that require extensive information exchanges between heterogeneous networks.

Purpose: Modulated electro-hyperthermia (mEHT), known as oncothermia, is an anticancer therapy that induces radiofrequency thermal damage to the cancer tissues. This study aimed to evaluate the potential effectiveness of mEHT as a therapeutic tool in ovarian and cervical cancer. Materials and methods: We used both tumor-bearing mice and ovarian and cervical OVCAR-3, SK-OV-3, HeLa and SNU-17 cancer cell lines to investigate the effects of mEHT in vivo and in vitro, respectively, and determine whether it was enhanced by cotreatment with an autophagy inhibitor. Results: We discovered that phosphorylation of p38, a stress-dependent kinase, was induced at the Thr180/Tyr182 residue in cancer cells exposed to mEHT. Apoptotic markers such as cleaved caspase-3 and poly-ADP ribose polymerase (PARP) were increased in OVCAR-3 and SNU-17 cells. Fluorescence-activated cell sorting (FACS) analysis showed a significant increase in the population of sub-G1 mEHT-exposed cells, which are dying and apoptotic cells. mEHT also reduced both weight and volume of xenograft tumors in mice transplanted with ovarian and cervical cancer cells and patient-derived cancer tissues. We determined that mEHT-induced cellular damage recovery was mediated by autophagy and, therefore, expectedly, cotreatment with mEHT and 3-methyladenine (3-MA), an autophagy inhibitor, more effectively inhibited cancer cell growth than individual treatment did. Conclusions: mEHT treatment alone was sufficient to inhibit cancer growth, while a combined treatment with mEHT and an autophagy inhibitor amplified this inhibition effect.

With the increasing number of social media users in recent years, news in various fields, such as politics, economics, and so on, can be easily accessed by users. However, most news spread through social networks including Twitter, Facebook, and Instagram has unknown sources, thus having a significant impact on news consumers. Fake news on COVID-19, which is affecting the global population, is propagating quickly and causes social disorder. Thus, a lot of research is being conducted on the detection of fake news on COVID-19 but is facing the problem of a lack of datasets. In order to alleviate the problem, we built a dataset on COVID-19 fake news from fact-checking websites in Korea and propose deep learning for detecting fake news on COVID-19 using the datasets. The proposed model is pre-trained with large-scale data and then performs transfer learning through a BiLSTM model. Moreover, we propose a method for initializing the hidden and cell states of the BiLSTM model to a [CLS] token instead of a zero vector. Through experiments, the proposed model showed that the accuracy is 78.8%, which was improved by 8% compared with the linear model as a baseline model, and that transfer learning can be useful with a small amount of data as we know it. A [CLS] token containing sentence information as the initial state of the BiLSTM can contribute to a performance improvement in the model.

The effect of feeding with taurine-enriched rotifers on larval growth and survival in the small yellow croaker Larimichthys polyactis was investigated. Rotifers, control (without taurine enrichment) or enriched with a commercial taurine supplement at two concentrations (400, and 800 mg/L), were used. The larvae (initial notochord length = 3.83 mm) were fed taurine-enriched rotifers in triplicate, from 3 days after hatching for 12 days. The average taurine contents of the rotifers were 0.31, 5.34, and 8.55 mg/g dry matter, respectively. The rotifers from all treatments had similar fatty acid composition. The growth and survival rates of the larvae fed rotifers enriched with 800 mg/L taurine supplementation were significantly higher than those of larvae fed rotifers without taurine enrichment (p = 0.005 and 0.002, respectively). The whole-body taurine content in the fish increased significantly with the increase in taurine level in the rotifers: 1.02, 3.48, and 4.11 mg/g in larvae fed control rotifers, and rotifers enriched with 400, and 800 mg/L taurine supplementation, respectively. The results of this study indicate that small yellow croaker larvae benefit from taurine concentrations above those typically reported in non-taurine-enriched rotifers.

Intracellular pathogens have evolved to utilize normal cellular processes to complete their replicative cycles. Pathogens that interface with proliferative cell signaling pathways risk infections that can lead to cancers, but the factors that influence malignant outcomes are incompletely understood. Human papillomaviruses (HPVs) predominantly cause benign hyperplasia in stratifying epithelial tissues. However, a subset of carcinogenic or "high-risk" HPV (hr-HPV) genotypes are etiologically linked to nearly 5% of all human cancers. Progression of hr-HPV-induced lesions to malignancies is characterized by increased expression of the E6 and E7 oncogenes and the oncogenic functions of these viral proteins have been widely studied. Yet, the mechanisms that regulate hr-HPV oncogene transcription and suppress their expression in benign lesions remain poorly understood. Here, we demonstrate that EGFR/MEK/ERK signaling, influenced by epithelial contact inhibition and tissue differentiation cues, regulates hr-HPV oncogene expression. Using monolayer cells, epithelial organotypic tissue models, and neoplastic tissue biopsy materials, we show that cell-extrinsic activation of ERK overrides cellular control to promote HPV oncogene expression and the neoplastic phenotype. Our data suggest that HPVs are adapted to use the EGFR/MEK/ERK signaling pathway to regulate their productive replicative cycles. Mechanistic studies show that EGFR/MEK/ERK signaling influences AP-1 transcription factor activity and AP-1 factor knockdown reduces oncogene transcription. Furthermore, pharmacological inhibitors of EGFR, MEK, and ERK signaling quash HPV oncogene expression and the neoplastic phenotype, revealing a potential clinical strategy to suppress uncontrolled cell proliferation, reduce oncogene expression and treat HPV neoplasia.

VP1, a pivotal capsid protein encoded by the foot-and-mouth disease virus (FMDV), plays an important role in receptor-mediated attachment and humoral immune responses. Previous studies show that amino acid changes in the VP1 protein of cell culture-adapted strains of FMDV alter the properties of the virus. In addition, FMDV VP1 modulates host IFN signal transduction. Here, we examined the ability of cell culture-adapted FMDV VP1(83K) and wild-type FMDV VP1(83E) to evade host immunity by blocking mitochondrial antiviral signaling protein (MAVS)/TNF Receptor Associated Factor 3 (TRAF3) mediated cellular innate responses. Wild-type FMDV VP1(83E) interacted specifically with C-terminal TRAF3-binding site within MAVS and this interaction inhibited binding of TRAF3 to MAVS, thereby suppressing interferon-mediated responses. This was not observed for cell culture-adapted FMDV VP1(83K). Finally, chimeric FMDV harboring VP1(83K) showed very low pathogenicity in pigs. Collectively, these data highlight a critical role of VP1 with respect to suppression of type-I IFN pathway and attenuation of FMDV by the E83K mutation in VP1.

On Jeju Island, South Korea, pigs have not been vaccinated against classical swine fever (CSF) since 1999. Analysis of bovine viral diarrhea virus (BVDV) isolated from pigs on Jeju Island between 2009 and 2019 identified five BVDV-1a strains and one BVDV-1b strain. These BVDV types were shown to be the same types as BVDV strains isolated from neighboring cow farms. BVDV antibody-positive pigs (both BVDV-1 and -2) were also detected at 54 of 168 pig farms during this period. In pig infection experiments using BVDV-1a and -2a strains isolated from neighboring cow farms, BVDV-1a was detected in the blood of one of four pigs infected at both 6 and 35 days post-infection (dpi) and in the blood of two of the four pigs at 28 dpi. Pigs showed higher anti-BVDV-1 titers (5.5 ± 1.5 log2) at 35 dpi. BVDV-2a was detected in the blood of one of four pigs infected with this virus at 28 dpi only, and lower antibody titers (2.75 ± 0.75 log2) were seen in these pigs at 35 dpi. While BVDV infection is not particularly pathogenic in pigs, it is still important to monitor porcine BVDV infections due to a differential diagnosis of CSFV.

Patient-derived xenografts (PDXs) are important in vivo models for the development of precision medicine. However, challenges exist regarding genetic alterations and relapse after primary treatment. Thus, PDX models are required as a new approach for preclinical and clinical studies. We established PDX models of gynecologic cancers and analyzed their clinical information. We subcutaneously transplanted 207 tumor tissues from patients with gynecologic cancer into nude mice from 2014 to 2019. The successful engraftment rate of ovarian, cervical, and uterine cancer was 47%, 64%, and 56%, respectively. The subsequent passages (P2 and P3) showed higher success and faster growth rates than the first passage (P1). Using gynecologic cancer PDX models, the tumor grade is a common clinical factor affecting PDX establishment. We found that the PDX success rate correlated with the patient’s prognosis, and also that ovarian cancer patients with a poor prognosis had a faster PDX growth rate (p < 0.0001). Next, the gene sets associated with inflammation and immune responses were shown in high-ranking successful PDX engraftment through gene set enrichment analysis and RNA sequencing. Up-regulated genes in successful engraftment were found to correlate with ovarian clear cell cancer patient outcomes via Gene Expression Omnibus dataset analysis.

The purpose of this study was to evaluate the effects of flavonoids and calcium phosphate ion clusters (CPIC) on dentin bonding stability. Seven experimental solutions were synthesized using icaritin (ICT), fisetin (FIS), silibinin (SIB), CPIC, and combinations of one of three flavonoids and CPIC (ICT + C, FIS + C, SIB + C). The experimental solutions were applied to demineralized dentin prior to the application of a universal adhesive. A group without any experimental solution served as a control. Dentin specimens pretreated with the experimental solutions were assayed using Fourier transform infrared (FTIR) spectroscopy. The microtensile bond strength (µTBS) and nanoleakage were evaluated at 24 h and after 10,000 thermocycles. FIS and ICT + C showed significantly higher µTBS than the control group at 24 h. CPIC, ICT + C, FIS + C, and SIB + C showed significantly higher µTBS than the control group after thermocycling. After thermocycling, silver infiltration into the hybrid layer and interfacial gaps was more noticeable in the control group than in the other groups. The FTIR spectra revealed the formation of apatitic minerals in the demineralized dentin in the flavonoid and CPIC combination groups. The pretreatment of demineralized dentin with flavonoids and CPIC improved dentin bonding stability. The flavonoid and CPIC combinations preserved dentin bond strength.

Fuel failure due to debris is a major cause of failure in pressurized water reactors. Fuel vendors have developed various filtering devices to reduce debris-induced failure and have evaluated filtering performance with their own test facilities and methods. Because of the different test facilities and methods, it is difficult to compare filtering performances objectively. This study presents an improved filtering test and an efficiency calculation method to fairly compare fuel-filtering efficiency regardless of the vendor's filtering features. To enhance the reliability of our evaluation, we established requirements for the test method and had a facility constructed according to the requirements. This article describes the debris specimens, the amount of debris, and the replicates for the proposed test method. A calculation method of comprehensive debris-filtering efficiency using a weighted mean is proposed. The test method was verified by repeated tests, and the tests were carried out using the PLUS7 and 17ACE7 test fuels to calculate the comprehensive debris-filtering efficiencies. The evaluation results revealed that the filtering performance of PLUS7 is better than that of 17ACE7. The proposed method can be used on any kind of debris-filtering devices and is appropriate for use as a standard. Keywords: Comprehensive Debris-Filtering Efficiency, Debris-Filtering Performance, Debris-Filtering Test, Debris-Induced Failure, Nuclear Fuel, Weighted Mean

ObjectiveThe main aim of this study was to evaluate cancer antigen 125 (CA125)/carcinoembryonic antigen (CEA) ratio (CCR), as a reliable marker to differentiate ovarian mucinous carcinoma from other epithelial ovarian carcinomas (EOCs), namely serous, clear cell, and endometrioid carcinomas.MethodsFemale patients suffering from different kinds of EOCs whom were subjected to elective surgery at the Gangnam Severance Hospital between January 2008 and December 2016, were included in this study. The serum levels of CA125 and CEA were assayed using commercially available kits per the manufacturer's instructions.ResultsThe CCR in mucinous carcinoma (mean 32.1) was significantly lower than that of clear cell (mean 235.0) and endometrioid carcinoma (mean 427.0) in stage I (all P

The number of ship accidents occurring in the Korean ocean has been steadily increasing year by year. The Korea Maritime Safety Tribunal (KMST) has published verdicts to ensure that the relevant personnel can share judgment on these accidents. As of 2020, there have been 3156 ship accidents; thus, it is difficult for the relevant personnel to study these various accidents by only reading the verdicts. Therefore, in this study, we propose a multi-task deep learning model with an attention mechanism for predicting the sentencing of ship accidents. The tasks are accident types, applied articles, and the sentencing of ship accidents. The proposed model was tested under verdicts published by the KMST between 2010 and 2019. Through experiments, we show that the proposed model can improve the performance of sentence prediction and can assist the relevant personnel to study these accidents.