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Abstract The effect of covering faces on face identification is recently garnering interest amid the COVID-19 pandemic. Here, we investigated how face identification performance was affected by two types of face disguise: sunglasses and face masks. Observers studied a series of faces; then judged whether a series of test faces, comprising studied and novel faces, had been studied before or not. Face stimuli were presented either without coverings (full faces), wearing sunglasses covering the upper region (eyes, eyebrows), or wearing surgical masks covering the lower region (nose, mouth, chin). We found that sunglasses led to larger reductions in sensitivity (d’) to face identity than face masks did, while both disguises increased the tendency to report faces as studied before, a bias that was absent for full faces. In addition, faces disguised during either study or test only (i.e. study disguised faces, test with full faces; and vice versa) led to further reductions in sensitivity from both studying and testing with disguised faces, suggesting that congruence between study and test is crucial for memory retrieval. These findings implied that the upper region of the face, including the eye-region features, is more diagnostic for holistic face-identity processing than the lower face region.

Abstract Mitochondrial dynamin-related protein 1 (Drp1) is a large GTPase regulator of mitochondrial dynamics and is known to play an important role in numerous pathophysiological processes. Despite being the most widely used Drp1 inhibitor, the specificity of Mdivi-1 towards human Drp1 has not been definitively proven and there have been numerous issues reported with its use including off-target effects. In our hands Mdivi-1 showed varying binding affinities toward human Drp1, potentially impacted by compound aggregation. Herein, we sought to identify a novel small molecule inhibitor of Drp1. From an initial virtual screening, we identified DRP1i27 as a compound which directly bound to the human isoform 3 of Drp1 via surface plasmon resonance and microscale thermophoresis. Importantly, DRP1i27 was found to have a dose-dependent increase in the cellular networks of fused mitochondria but had no effect in Drp1 knock-out cells. Further analogues of this compound were identified and screened, though none displayed greater affinity to human Drp1 isoform 3 than DRP1i27. To date, this is the first small molecule inhibitor shown to directly bind to human Drp1.

Abstract Late Holocene relative sea-level (RSL) data are important to understand the drivers of RSL change, but there is a lack of precise RSL records from the Sunda Shelf. Here, we produced a Late Holocene RSL reconstruction from coral microatolls in Singapore, demonstrating for the first time the utility of Diploastrea heliopora microatolls as sea-level indicators. We produced 12 sea-level index points and three marine limiting data with a precision of

Abstract The prevalence of depression may be affected by changes in psychiatric practices and the availability of online mental health information in the past two decades. This study aimed to evaluate the aggregate prevalence of depression in communities from different countries between 1994 and 2014 and to explore the variations in prevalence stratified by geographical, methodological and socio-economic factors. A total of 90 studies were identified and met the inclusion criteria (n = 1,112,573 adults) with 68 studies on single point prevalence, 9 studies on one-year prevalence, and 13 studies on lifetime prevalence of depression. A random-effects model meta-analysis that was performed to calculate the aggregate point, one-year and lifetime prevalence of depression calculated prevalences of 12.9%, 7.2% and 10.8% respectively. Point prevalence of depression was significantly higher in women (14.4%), countries with a medium human development index (HDI) (29.2%), studies published from 2004 to 2014 (15.4%) and when using self-reporting instruments (17.3%) to assess depression. Heterogeneity was identified by meta-regression and subgroup analysis, and response rate, percentage of women and year of publication, respectively, were determined contribute to depression prevalence. This meta-analysis allows benchmarking of the prevalence of depression during the era when online health information emerged, facilitating future comparisons.

Notwithstanding the latest advancements in anticancer therapy, non-small cell lung cancer (NSCLC) remains a prominent contributor to cancer-associated mortality worldwide. Therefore, effective anti-cancer agents are required for the treatment of NSCLC. We previously demonstrated that the natural alkaloid evodiamine efficiently suppressed lung cancer cells and lung cancer stem-like cell populations by suppressing heat shock protein 70 (Hsp70). This finding inspired us to formulate evodiamine-based anti-cancer compounds against NSCLC. In this study, we synthesized a series of evodiamine derivatives with substitutions at the N14 position. EV206 was chosen for further study because it was the most effective among the 22 evodiamine derivatives at stopping H1299 cell growth. EV206 treatment efficiently suppressed cell viability and colony formation in both attached cells and in soft agar, even in those carrying drug resistance, by inducing apoptosis. The effectiveness of EV206 is approximately ten times greater than that of evodiamine. Normal cell viability was marginally affected by EV206 treatment. Additionally, EV206 efficiently decreased the cancer stem cell (CSC) population in the NSCLC cells. EV206 reduced the growth of H460 xenograft tumors without exhibiting toxic effects. These data implied that EV206 has the potential to be an effective Hsp70-targeting anticancer drug with low toxicity., (© 2024. The Author(s).)

This study investigated neurodevelopment and risk factors in children surgically treated for congenital gastrointestinal anomalies (CGIA), excluding those with known high-risk factors such as low birth weight or chromosomal anomalies. Data of children born between 2008 and 2015 who underwent surgical treatment for CGIA were retrieved from the Korean National Health Insurance Database. CGIA included esophageal atresia, duodenal atresia, jejunoileal atresia, anorectal malformations, and congenital megacolon. Neurodevelopmental impairment (NDI) was defined as Korean Ages and Stages Questionnaire scores below the determined cut-off or Korean Developmental Screening Test scores < 2 standard deviations at 3 years of age. Children with CGIA had a significantly higher risk of NDI than controls (6.2% vs. 2.7%, p < 0.001). Growth failure was correlated with NDI. Longer durations of oxygen support (adjusted odds ratio [aOR], 1.037; 95% confidence interval [CI], 1.013-1.063), mechanical ventilation (aOR, 1.053; 95% CI, 1.018-1.089), and number of surgeries (aOR, 1.137; 95% CI, 1.016-1.273) were significantly associated with NDI. These findings emphasize that cautious yet proactive neurodevelopmental monitoring is crucial in affected children, ensuring timely intervention and that excessive concern among families is unnecessary., (© 2024. The Author(s).)

The misuse and overtreatment of antibiotics in hospitalized patients with community-acquired pneumonia (CAP) can cause multi-drug resistance and worsen clinical outcomes. We aimed to analyze the trends and appropriateness of antibiotic changes in hospitalized patients with CAP and their impact on clinical outcomes. This retrospective study enrolled patients with CAP, aged > 18 years, admitted from January 2017 to December 2021 at Seoul National University Bundang Hospital, South Korea. We examined the pathogens identified, antibiotics prescribed, and the appropriateness of antibiotic changes as reviewed by infectious disease specialists. Antibiotic appropriateness was assessed based on adherence to the 2019 ATS/IDSA guidelines and the 2018 Korean national guidelines for CAP, targeting appropriate pathogens, proper route, dosage, and duration of therapy. Outcomes measured included time to clinical stability (TCS), length of hospital stay, duration of antibiotic treatment, and in-hospital mortality. The study included 436 patients with a mean age of 72.11 years, of whom 35.1% were male. The average duration of antibiotic treatment was 13.5 days. More than 55% of patients experienced at least one antibiotic change, and 21.7% had consecutive changes. Throughout their hospital stay, 273 patients (62.6%) received appropriate antibiotic treatment, while 163 patients (37.4%) received at least one inappropriate antibiotic prescription. Those who received at least one inappropriate prescription experienced longer antibiotic treatment durations and extended hospital stays, despite having similar TCS. In conclusion, inappropriate antibiotic prescribing in hospitalized patients with CAP is associated with prolonged antibiotic treatment and increased length of stay. Emphasizing the appropriate initial antibiotic selection may help mitigate these negative effects., (© 2024. The Author(s).)

Intravesical treatment using either reovirus or natural killer (NK) cells serves as an efficient strategy for the treatment of bladder cancer cells (BCCs); however, corresponding monotherapies have often shown modest cytotoxicity. The potential of a locoregional combination using high-dose reovirus and NK cell therapy in an intravesical approach has not yet been studied. In this study, we evaluated the effectiveness of reoviruses and expanded NK cells (eNK) as potential strategies for the treatment of bladder cancer. The anti-tumor effects of mono-treatment with reovirus type 3 Dearing strain (RC402 and RP116) and in combination with interleukin (IL)-18/-21-pretreated eNK cells were investigated on BCC lines (5637, HT-1376, and 253J-BV) using intravesical therapy to simulate in vitro model. RP116 and IL-18/-21-pretreated eNK cells exhibited effective cytotoxicity against grade 1 carcinoma (5637 cells) when used alone, but not against HT-1376 (grade 2 carcinoma) and 253J-BV cells (derived from a metastatic site). Notably, combining RP116 with IL-18/-21-pretreated eNK cells displayed effective cytotoxicity against both HT-1376 and 253J-BV cells. Our findings underscore the potential of a combination therapy using reoviruses and NK cells as a promising strategy for treating bladder cancer., (© 2024. The Author(s).)

When individuals listen to speech, their neural activity phase-locks to the slow temporal rhythm, which is commonly referred to as "neural tracking". The neural tracking mechanism allows for the detection of an attended sound source in a multi-talker situation by decoding neural signals obtained by electroencephalography (EEG), known as auditory attention decoding (AAD). Neural tracking with AAD can be utilized as an objective measurement tool for diverse clinical contexts, and it has potential to be applied to neuro-steered hearing devices. To effectively utilize this technology, it is essential to enhance the accessibility of EEG experimental setup and analysis. The aim of the study was to develop a cost-efficient neural tracking system and validate the feasibility of neural tracking measurement by conducting an AAD task using an offline and real-time decoder model outside the soundproof environment. We devised a neural tracking system capable of conducting AAD experiments using an OpenBCI and Arduino board. Nine participants were recruited to assess the performance of the AAD using the developed system, which involved presenting competing speech signals in an experiment setting without soundproofing. As a result, the offline decoder model demonstrated an average performance of 90%, and real-time decoder model exhibited a performance of 78%. The present study demonstrates the feasibility of implementing neural tracking and AAD using cost-effective devices in a practical environment., (© 2023. The Author(s).)

Three-dimensional (3D) printing allows the fabrication of complex shapes with high resolutions. However, the printed structures typically have fixed shapes and functions. Four-dimensional printing allows the shapes of 3D-printed structures to be transformed in response to external stimuli. Among the external stimuli, light has unique advantages for remote thermal actuation. However, light absorption in opaque structures occurs only near the sample surface; thus, actuation can be slow. Here, we propose and experimentally demonstrate the rapid and selective actuation of 3D-printed shape-memory polymer (SMP) composites using microwave heating. The SMP composite filaments are prepared using different amounts of graphite flakes. Microwave radiation can penetrate the entire printed structures and induce rapid heating. With sufficient graphite contents, the printed SMP composites are heated above their glass transition temperature within a few seconds. This leads to rapid thermal actuation of the 3D-printed SMP structures. Finally, dual-material 3D printing is demonstrated to induce selective microwave heating and control actuation motion. Our experiments and simulations indicate that microwave heating of SMP composites can be an effective method for the rapid and selective actuation of complex structures., (© 2023. Springer Nature Limited.)

Renal tubule has distinct metabolic features and functional activity that may be altered during kidney disease. In this paper, we present label-free functional activity imaging of renal tubule in normal and obstructed mouse kidney models using three-dimensional (3D) dynamic optical coherence tomography (OCT) ex vivo. To create an obstructed kidney model, we ligated the ureter of the left kidney for either 7 or 14 days. Two different dynamic OCT (DOCT) methods were implemented to access the slow and fast activity of the renal tubules: a logarithmic intensity variance (LIV) method and a complex-correlation-based method. Three-dimensional DOCT data were acquired with a 1.3 [Formula: see text]m swept-source OCT system and repeating raster scan protocols. In the normal kidney, the renal tubule appeared as a convoluted pipe-like structure in the DOCT projection image. Such pipe-like structures were not observed in the kidneys subjected to obstruction of the ureter for several days. Instead of any anatomical structures, a superficial high dynamics appearance was observed in the perirenal cortex region of the obstructed kidneys. These findings suggest that volumetric LIV can be used as a tool to investigate kidney function during kidney diseases., (© 2023. Springer Nature Limited.)

Methylation patterns in cell-free DNA (cfDNA) have emerged as a promising genomic feature for detecting the presence of cancer and determining its origin. The purpose of this study was to evaluate the diagnostic performance of methylation-sensitive restriction enzyme digestion followed by sequencing (MRE-Seq) using cfDNA, and to investigate the cancer signal origin (CSO) of the cancer using a deep neural network (DNN) analyses for liquid biopsy of colorectal and lung cancer. We developed a selective MRE-Seq method with DNN learning-based prediction model using demethylated-sequence-depth patterns from 63,266 CpG sites using SacII enzyme digestion. A total of 191 patients with stage I-IV cancers (95 lung cancers and 96 colorectal cancers) and 126 noncancer participants were enrolled in this study. Our study showed an area under the receiver operating characteristic curve (AUC) of 0.978 with a sensitivity of 78.1% for colorectal cancer, and an AUC of 0.956 with a sensitivity of 66.3% for lung cancer, both at a specificity of 99.2%. For colorectal cancer, sensitivities for stages I-IV ranged from 76.2 to 83.3% while for lung cancer, sensitivities for stages I-IV ranged from 44.4 to 78.9%, both again at a specificity of 99.2%. The CSO model's true-positive rates were 94.4% and 89.9% for colorectal and lung cancers, respectively. The MRE-Seq was found to be a useful method for detecting global hypomethylation patterns in liquid biopsy samples and accurately diagnosing colorectal and lung cancers, as well as determining CSO of the cancer using DNN analysis.Trial registration: This trial was registered at ClinicalTrials.gov (registration number: NCT04253509) for lung cancer on 5 February 2020, https://clinicaltrials.gov/ct2/show/NCT04253509 . Colorectal cancer samples were retrospectively registered at CRIS (Clinical Research Information Service, registration number: KCT0008037) on 23 December 2022, https://cris.nih.go.kr , https://who.init/ictrp . Healthy control samples were retrospectively registered., (© 2023. Springer Nature Limited.)

DNA methylation is an epigenetic modification that regulates gene expression and plays an essential role in hematopoiesis. UHRF1 and DNMT1 are both crucial for regulating genome-wide maintenance of DNA methylation. Specifically, it is well known that hypermethylation is crucial characteristic of acute myeloid leukemia (AML). However, the mechanism underlying how DNA methylation regulates the differentiation of AML cells, including THP-1 is not fully elucidated. In this study, we report that UHRF1 or DNMT1 depletion enhances the phorbol-12-myristate-13-acetate (PMA)-induced differentiation of THP-1 cells. Transcriptome analysis and genome-wide methylation array results showed that depleting UHRF1 or DNMT1 induced changes that made THP-1 cells highly sensitive to PMA. Furthermore, knockdown of UHRF1 or DNMT1 impeded solid tumor formation in xenograft mouse model. These findings suggest that UHRF1 and DNMT1 play a pivotal role in regulating differentiation and proliferation of THP-1 cells and targeting these proteins may improve the efficiency of differentiation therapy in AML patients., (© 2023. Springer Nature Limited.)

Posttransplantation diabetes mellitus (PTDM) is an important metabolic complication after KT that causes graft failure and cardiovascular complications in kidney transplantation (KT) recipients. Using the national claim data of South Korea, 7612 KT recipients between 2009 and 2017 were analyzed. PTDM was defined as a consecutive 30-day prescription history of antidiabetic medication after KT. Among these patients, 24.7% were diagnosed with PTDM, and 51.9% were diagnosed within 6 months after KT. Compared to patients without PTDM, those with PTDM were older, more likely to be men, more likely to be diagnosed with hypertension and cardio-cerebrovascular disease, and experienced more rejection episodes requiring high-dose steroid treatment after KT. During the follow-up, 607 DCGFs, 230 DWGFs, 244 MACEs, and 260 all-cause mortality events occurred. Patients with PTDM showed a higher risk of DCGF (adjusted hazard ratio [aHR] 1.49; 95% confidence interval [CI] 1.22-1.82; P < 0.001) and MACEs (aHR 1.76; 95% CI 1.33-2.31; P < 0.001) than patients without PTDM. The risks for all clinical outcomes were higher in the insulin group than in the non-use insulin group. PTDM in KT recipients resulted in both worse allograft and patient outcomes represented by DCGF and MACE, especially in patients needing insulin treatment., (© 2022. The Author(s).)

Dysbiosis of the oral microbiota plays an important role in the progression of periodontitis, which is characterized by chronic inflammation and alveolar bone loss, and associated with systemic diseases. Bacterial extracellular vesicles (EVs) contain various bioactive molecules and show diverse effects on host environments depending on the bacterial species. Recently, we reported that EVs derived from Filifactor alocis, a Gram-positive periodontal pathogen, had osteoclastogenic activity. In the present study, we analysed the osteoclastogenic potency and immunostimulatory activity of EVs derived from the Gram-negative periodontal pathogens Porphyromonas gingivalis and Tannerella forsythia, the oral commensal bacterium Streptococcus oralis, and the gut probiotic strain Lactobacillus reuteri. Bacterial EVs were purified by density gradient ultracentrifugation using OptiPrep (iodixanol) reagent. EVs from P. gingivalis, T. forsythia, and S. oralis increased osteoclast differentiation and osteoclstogenic cytokine expression in osteoclast precursors, whereas EVs from L. reuteri did not. EVs from P. gingivalis, T. forsythia, and S. oralis preferentially activated Toll-like receptor 2 (TLR2) rather than TLR4 or TLR9, and induced osteoclastogenesis mainly through TLR2. The osteoclastogenic effects of EVs from P. gingivalis and T. forsythia were reduced by both lipoprotein lipase and polymyxin B, an inhibitor of lipopolysaccharide (LPS), while the osteoclastogenic effects of EVs from S. oralis were reduced by lipoprotein lipase alone. These results demonstrate that EVs from periodontal pathogens and oral commensal have osteoclastogenic activity through TLR2 activation by lipoproteins and/or LPS., (© 2022. The Author(s).)

Gasoline direct injection (GDI) engines emit less carbon dioxide (CO 2 ) than port fuel injection (PFI) engines when fossil fuel conditions are the same. However, GDI engines emit more ultrafine particulate matter, which can have negative health effects, leading to particulate emission regulations. To satisfy these regulations, various studies have been done to reduce particulate matter, and several studies focused on lubricants. This study focuses on the influence of lubricant on the formation of particulate matter and its effect on particulate emissions in GDI engines. An instrumented, combustion and optical singe-cylinder GDI engine fueled by four different lubricant-gasoline blends was used with various injection conditions. Combustion experiments were used to determine combustion characteristics, and gaseous emissions indicated that the lubricant did not influence mixture homogeneity but had an impact on unburned fuels. Optical experiments showed that the lubricant did not influence spray but did influence wall film formation during the injection period, which is a major factor affecting particulate matter generation. Particulate emissions indicated that lubricant included in the wall film significantly affected PN emissions depending on injection conditions. Additionally, the wall film influenced by the lubricant affected the overall particle size and its distribution., (© 2022. The Author(s).)

Spoof surface plasmons in corrugated metal surfaces allow tight field confinement and guiding even at low frequencies and are promising for compact microwave photonic devices. Here, we use metal-ink printing on flexible substrates to construct compact spoof plasmon resonators. We clearly observe multipole resonances in the microwave frequencies and demonstrate that they are still maintained even under significant bending. Moreover, by combining two resonators of slightly different sizes, we demonstrate spectral filtering via the Vernier effect. We selectively address a target higher-order resonance while suppressing the other modes. Finally, we investigate the index-sensing capability of printed plasmonic resonators. In the Vernier structure, we can control the resonance amplitude and frequency by adjusting a resonance overlap between two coupled resonators. The transmission amplitude can be maximized at a target refractive index, and this can provide more functionalities and increased design flexibility. The metal-ink printing of microwave photonic structures can be applied to various flexible devices. Therefore, we expect that the compact, flexible plasmonic structures demonstrated in this study may be useful for highly functional elements that can enable tight field confinement and manipulation., (© 2021. The Author(s).)

Interactions between the endoplasmic reticulum (ER) and mitochondria (Mito) are crucial for many cellular functions, and their interaction levels change dynamically depending on the cellular environment. Little is known about how the interactions between these organelles are regulated within the cell. Here we screened a compound library to identify chemical modulators for ER-Mito contacts in HEK293T cells. Multiple agonists of G-protein coupled receptors (GPCRs), beta-adrenergic receptors (β-ARs) in particular, scored in this screen. Analyses in multiple orthogonal assays validated that β2-AR activation promotes physical and functional interactions between the two organelles. Furthermore, we have elucidated potential downstream effectors mediating β2-AR-induced ER-Mito contacts. Together our study identifies β2-AR signaling as an important regulatory pathway for ER-Mito coupling and highlights the role of these contacts in responding to physiological demands or stresses., (© 2021. The Author(s).)

Circulating tumor DNA (ctDNA) may reveal dynamic tumor status during therapy. We conducted serial ctDNA analysis to investigate potential association with clinical outcome in metastatic colorectal cancer (mCRC) patients receiving chemotherapy. Tissue KRAS/NRAS wild-type mCRC patients were enrolled and treated with first-line cetuximab-containing chemotherapy. ctDNA isolated from plasma were analyzed by next generation sequencing (NGS) with 16 targeted gene panel. Among 93 patients, 84 (90.3%) had at least 1 somatic mutation in baseline ctDNA samples (average 2.74). Five patients with KRAS or NRAS hotspot mutation in the ctDNA showed significantly worse progression-free survival (PFS) (p = 0.029). Changes in average variant allele frequency (VAF) in ctDNA showed significant correlation with tumor size change at the time of first response evaluation (p = 0.020) and progressive disease (PD) (p = 0.042). Patients whose average VAF decreased below cutoff (< 1%) at the first evaluation showed significantly better PFS (p < 0.001), and the average VAF change further discriminated the PFS in the patients in partial response (p = 0.018). At the time of PD, 54 new mutations including KRAS and MAP2K1 emerged in ctDNA. ctDNA sequencing can provide mutation profile that could better reflect tumor mutation status and predict treatment outcome., (© 2021. The Author(s).)

Polyunsaturated fatty acids (PUFA) are important for neuronal function and may contribute to the development of neurodegenerative diseases. Here, we investigated the correlation between dietary intake and plasma concentrations of PUFA and their associations with clinical severity in early-stage Parkinson's disease (PD). In a case-control study with 38 patients with PD and 33 controls, we assessed dietary intake using food frequency questionnaires and simultaneously measured the plasma levels of five PUFA. No differences were observed in dietary total energy and lipid intake, including PUFA, between patients with PD and controls. However, α-linolenic acid (ALA), linoleic acid (LA), and arachidonic acid (AA) plasma levels were lower in patients with PD. The association between dietary intake and plasma PUFA concentrations was not significant in patients with PD. ALA and LA plasma levels were inversely correlated with motor severity in patients with PD, while docosahexaenoic acid and AA plasma levels were positively correlated with non-motor symptoms after controlling for age and sex.

Transcriptome expression reflects genetic response in diverse conditions. In this study, RNA sequencing was utilized to profile multiple tissues such as liver, breast, caecum, and gizzard of Korean commercial chicken raised in Korea and Kyrgyzstan. We analyzed ten samples per tissue from each location to identify candidate genes which are involved in the adaptation of Korean commercial chicken to Kyrgyzstan. At false discovery rate (FDR) < 0.05 and fold change (FC) > 2, we found 315, 196, 167 and 198 genes in liver, breast, cecum, and gizzard respectively as differentially expressed between the two locations. GO enrichment analysis showed that these genes were highly enriched for cellular and metabolic processes, catalytic activity, and biological regulations. Similarly, KEGG pathways analysis indicated metabolic, PPAR signaling, FoxO, glycolysis/gluconeogenesis, biosynthesis, MAPK signaling, CAMs, citrate cycles pathways were differentially enriched. Enriched genes like TSKU, VTG1, SGK, CDK2 etc. in these pathways might be involved in acclimation of organisms into diverse climatic conditions. The qRT-PCR result also corroborated the RNA-Seq findings with R 2 of 0.76, 0.80, 0.81, and 0.93 for liver, breast, caecum, and gizzard respectively. Our findings can improve the understanding of environmental acclimation process in chicken.

The genus Kordia is one of many genera affiliated with the family Flavobacteriaceae of the phylum Bacteroidetes, well known for its degradation of high molecular weight organic matters. The genus Kordia currently comprises eight species, type strains of which have been isolated from a diverse range of marine environments. As of this report, four genome sequences have been submitted for cultured strains of Kordia, but none are complete nor have they been analyzed comprehensively. In this study, we report the complete genome of Kordia antarctica IMCC3317 T , isolated from coastal seawater off the Antarctic Peninsula. The complete genome of IMCC3317 T consists of a single circular chromosome with 5.5 Mbp and a 33.2 mol% of G+C DNA content. The IMCC3317 T genome showed features typical of chemoheterotrophic marine bacteria and similar to other Kordia genomes, such as complete gene sets for the Embden-Meyerhof-Parnas glycolysis pathway, tricarboxylic acid cycle and oxidative phosphorylation. The genome also encoded many carbohydrate-active enzymes, some of which were clustered into approximately seven polysaccharide utilization loci, thereby demonstrating the potential for polysaccharide utilization. Finally, a nosZ gene encoding nitrous oxide reductase, an enzyme that catalyzes the reduction of N 2 O to N 2 gas, was also unique to the IMCC3317 T genome.

Thyroid nodules are initially handled by fine needle aspiration (FNA). However, the stance of thyroid core needle biopsy (CNB) still is a challenge. This study aimed to compare the diagnostic performances and conclusive rates of FNA and CNB for the diagnosis of thyroid nodules and to define effective indications of CNB. This retrospective study enrolled 1,060 consecutive thyroid nodules in 1,037 patients who underwent FNA from January 2008 to May 2008, and 462 consecutive nodules in 453 patients who underwent CNB from January 2014 to December 2015 at our institution. Ultrasound (US) features were classified according to the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) and Korean TIRADS (K-TIRADS). We compared diagnostic performances and conclusive rates between FNA and CNB groups. Propensity score matching was conducted to match FNA patients with CNB patients. After matching, the diagnostic performances for selecting surgical candidates and predicting malignancy were comparable between the two biopsy groups. Based on US findings, conclusive results were obtained significantly more in CNB than in FNA when thyroid nodules were classified as ACR TI-RADS or K-TIRADS category 4 and measured larger than 2 cm. Diagnostic performances between FNA and CNB were comparable. Superiority of CNB to FNA was found for thyroid nodules larger than 2 cm and classified as ACR TI-RADS or K-TIRADS category 4.

In light of recent developments in genomic technology and the rapid accumulation of genomic information, a major transition toward precision medicine is anticipated. However, the clinical applications of genomic information remain limited. This lag can be attributed to several complex factors, including the knowledge gap between medical experts and bioinformaticians, the distance between bioinformatics workflows and clinical practice, and the unique characteristics of genomic data, which can make interpretation difficult. Here we present a novel genomic data model that allows for more interactive support in clinical decision-making. Informational modelling was used as a basis to design a communication scheme between sophisticated bioinformatics predictions and the representative data relevant to a clinical decision. This study was conducted by a multidisciplinary working group who carried out clinico-genomic workflow analysis and attribute extraction, through Failure Mode and Effects Analysis (FMEA). Based on those results, a clinical genome data model (cGDM) was developed with 8 entities and 46 attributes. The cGDM integrates reliability-related factors that enable clinicians to access the reliability problem of each individual genetic test result as clinical evidence. The proposed cGDM provides a data-layer infrastructure supporting the intellectual interplay between medical experts and informed decision-making.

Eye-hand span, i.e., the distance between a performer's fixation and execution of a note, has been regarded as a decisive indicator of performers' competence in sight-reading. However, integrated perspectives regarding the relationship between eye-hand span and sight-reading variables have been less discussed. The present study explored the process of sight-reading in terms of three domains and their interrelations. The domain indicators included musical complexity and playing tempo (musical domain), eye-hand span (cognitive domain), and performance accuracy (behavioural domain). Thirty professional pianists sight-read four musical pieces with two different complexities and playing tempi. We measured the participants' eye-hand span, evaluated their performance accuracy, and divided the participants into three groups according to their performance accuracy values. Interestingly, we found that the eye-hand span did not change solely based on the performance accuracy. In contrast, the relationship between the eye-hand span and performance accuracy changed according to the difficulty of the sight-reading task. Our results demonstrate that the eye-hand span is not a decisive indicator of sight-reading proficiency but is a strategy that can vary according to the difficulty of sight-reading tasks. Thus, proficient sight-readers are performers who are skilled at adjusting their eye-hand span instead of always maintaining an extended span.

With the increased risk of cardiovascular disease, the use of botanicals for vascular endothelial dysfunction has intensified. Here, we explored the synergistic mechanisms of Sanghuang-Danshen (SD) phytochemicals on the homeostatic protection against high-fat-induced vascular dysfunction in healthy subjects, using a network biology approach, based on a randomised crossover clinical trial. Seventeen differential markers identified in blood samples taken at 0, 3 and 6 h post-treatment, together with 12SD phytochemicals, were mapped onto the network platform, termed the context-oriented directed associations. The resulting vascular sub-networks illustrated associations between 10 phytochemicals with 32 targets implicated in 143 metabolic/signalling pathways. The three key events included adhesion molecule production (ellagic acid, fumaric acid and cryptotanshinone; VCAM-1, ICAM-1 and PLA2G2A; fatty acid metabolism), platelet activation (ellagic acid, protocatechuic acid and tanshinone IIA; VEGFA, APAF1 and ATF3; mTOR, p53, Rap1 and VEGF signalling pathways) and endothelial inflammation (all phytochemicals, except cryptotanshinone; 29 targets, including TP53 and CASP3; MAPK and PI3K-Akt signalling pathways, among others). Our collective findings demonstrate a potential of SD to protect unintended risks of vascular dysfunction in healthy subjects, providing a deeper understanding of the complicated synergistic mechanisms of signature phytochemicals in SD.

A hybrid resistor has been fabricated by parallely connecting carbon nanotube (CNT) fiber with negative temperature coefficient of resistance (TCR) and metal alloy with positive TCR to achieve near zero TCR. The CNT fibers were prepared by yarning CNTs grown on the silicone substrate by chemical vapor deposition (CVD) method. The CNT fiber resistors were fabricated by winding CNT fiber on the ceramic rod. Metal terminals were connected at both ends of the CNT fiber wound on the ceramic rod. The metal alloy resistors were fabricated with copper (Cu) and nickel (Ni) with different weight compositions. Electrical resistance and thermal stability (in terms of TCR in this work) of the CNT fiber resistors, the metal alloy resistors, and the hybrid resistors were measured as 7.94 Ω and -870 ppm/°C, 7.94 Ω and 1100 ppm/°C, and 3.97 Ω and -2 ppm/°C, respectively. In case of parallelly connected resistors with suitable combination, the resistance was lower than that of resistor with lower value, and the TCR approached to near zero. Finally, we propose a theoretical approach for adjusting resistance and TCR of the hybrid resistor composed of metal alloy and CNT fibers.

We report a novel transcriptomic analysis workflow called LiEB (Life cycle of Epstein-Barr virus) to characterize distributions of oncogenic virus, Epstein-Barr virus (EBV) infection in human tumors. We analyzed 851 The Cancer Genome Atlas whole-transcriptome sequencing (WTS) data to investigate EBV infection by life cycle information using three-step LiEB workflow: 1) characterize virus infection generally; 2) align transcriptome sequences against a hybrid human-EBV genome, and 3) quantify EBV gene expression. Our results agreed with EBV infection status of public cell line data. Analysis in stomach adenocarcinoma identified EBV-positive cases involving PIK3CA mutations and/or CDKN2A silencing with biologically more determination, compared to previous reports. In this study, we found that a small number of colorectal adenocarcinoma cases involved with EBV lytic gene expression. Expression of EBV lytic genes was also observed in 3% of external colon cancer cohort upon WTS analysis. Gene set enrichment analysis showed elevated expression of genes related to E2F targeting and interferon-gamma responses in EBV-associated tumors. Finally, we suggest that interpretation of EBV life cycle is essential when analyzing its infection in tumors, and LiEB provides high capability of detecting EBV-positive tumors. Observation of EBV lytic gene expression in a subset of colon cancers warrants further research.

Benzofuran derivatives have wide range of biological activities as anti-oxidant, anti-inflammatory and anticonvulsant agent. In this study, we investigated whether the novel benzofuran derivative, DK-1014 has the anti-inflammatory effects on macrophage and lung epithelial cells and anti-asthmatic effects on ovalbumin-treated mice. A series of 2-arylbenzofuran analogues were synthesized and evaluated for NO and interleukin-6 (IL-6) inhibition in LPS-stimulated Raw264.7 cells. Of these analogues, compounds 8, 22a, 22d, and 22 f (DK-1014) exhibited notable inhibitory activity with respect to IL-6 and NO production. In particular, compound DK-1014 strongly reduced IL-6, IL-8, and MMP-9 mRNA expression and IL-6, IL-8, and MCP-1 production in phorbol myristate acetate stimulated A549 cells, reduced MAPKs phosphorylation and c-fos translocation, and attenuated AKT, p70S6K and GSK phosphorylation. In vivo experiments were also performed on ovalbumin-sensitized and challenged BALB/c mice. DK-1014 reduced the airway hyperresponsiveness, inflammatory cell counts and cytokine levels (IL-4, 5, 13) in bronchial alveolar lavage fluid (BALF) and immunoglobulin E in serum, and attenuated inflammatory cell infiltration and mucus hypersecretion in lung tissue. These findings indicate that DK-1014 can protect against allergic airway inflammation through the AP-1 and AKT/mTOR pathways and could be useful source for the development of a therapeutic agent for asthma.

Early brain development requires a tight orchestration between neural tube patterning and growth. How pattern formation and brain growth are coordinated is incompletely understood. Previously we showed that aristaless-related homeobox (ARX), a paired-like transcription factor, regulates cortical progenitor pool expansion by repressing an inhibitor of cell cycle progression. Here we show that ARX participates in establishing dorsoventral identity in the mouse forebrain. In Arx mutant mice, ventral genes, including Olig2, are ectopically expressed dorsally. Furthermore, Gli1 is upregulated, suggesting an ectopic activation of SHH signaling. We show that the ectopic Olig2 expression can be repressed by blocking SHH signaling, implicating a role for SHH signaling in Olig2 induction. We further demonstrate that the ectopic Olig2 accounts for the reduced Pax6 and Tbr2 expression, both dorsal specific genes essential for cortical progenitor cell proliferation. These data suggest a link between the control of dorsoventral identity of progenitor cells and the control of their proliferation. In summary, our data demonstrate that ARX functions in a gene regulatory network integrating normal forebrain patterning and growth, providing important insight into how mutations in ARX can disrupt multiple aspects of brain development and thus generate a wide spectrum of neurodevelopmental phenotypes observed in human patients.

Here we report a photonic annealing process for yttria-stabilized zirconia films, which are one of the most well-known solid-state electrolytes for solid oxide fuel cells (SOFCs). Precursor films were coated using a wet-chemical method with a simple metal-organic precursor solution and directly annealed at standard pressure and temperature by two cycles of xenon flash lamp irradiation. The residual organics were almost completely decomposed in the first pre-annealing step, and the fluorite crystalline phases and good ionic conductivity were developed during the second annealing step. These films showed properties comparable to those of thermally annealed films. This process is much faster than conventional annealing processes (e.g. halogen furnaces); a few seconds compared to tens of hours, respectively. The significance of this work includes the treatment of solid-state electrolyte oxides for SOFCs and the demonstration of the feasibility of other oxide components for solid-state energy devices.

The juice of Ageratum houstonianum is used in folk medicine as an external wound healing aid for skin injuries. However, the active component of A. houstonianum and its mode of action in skin wound healing has not been investigated. This study was conducted to investigate the effect of A. houstonianum ethanolnolic extract (AHE) on the expression of aquaporin-3 (AQP3), an integral membrane protein for water and glycerol transport in keratinocytes, and to identify the structure of the A. houstonianum bioactive compound. Here, we show that AHE increased AQP3 gene expression at the transcriptional level through the p38 MAPK pathway in HaCaT cells. Furthermore, AHE ameliorated suppression of AQP3 expression caused by ultraviolet B (UVB) irradiation. Agerarin (6,7-dimethoxy-2,2-dimethyl-2H-chromene) was identified as the bioactive compound responsible for the up-regulation of AQP3 expression by enhancing the expression of the transcription factor circadian locomotor output cycles kaput (CLOCK). In conclusion, agerarin is a bioactive compound in AHE responsible for CLOCK-mediated AQP3 expression in keratinocytes.

Saliva has attracted attention as a diagnostic fluid due to the association of oral microbiota with systemic diseases. However, the lack of standardised methods for saliva collection has led to the slow uptake of saliva in microbiome research. The aim of this study was to systematically evaluate the potential effects on salivary microbiome profiles using different methods of saliva collection, storage and gDNA extraction. Three types of saliva fractions were collected from healthy individuals with or without the gDNA stabilising buffer. Subsequently, three types of gDNA extraction methods were evaluated to determine the gDNA extraction efficiencies from saliva samples. The purity of total bacterial gDNA was evaluated using the ratio of human β-globin to bacterial 16S rRNA PCR while 16S rRNA gene amplicon sequencing was carried out to identify the bacterial profiles present in these samples. The quantity and quality of extracted gDNA were similar among all three gDNA extraction methods and there were no statistically significant differences in the bacterial profiles among different saliva fractions at the genus-level of taxonomic classification. In conclusion, saliva sampling, processing and gDNA preparation do not have major influence on microbiome profiles.

This study aimed to evaluate whether the relationship between obesity and erosive reflux disease (ERD) is mediated by cardiometabolic risk factors. This cohort study included subjects who underwent repeated endoscopy. To assess whether the association between body mass index (BMI) and ERD development was mediated by cardiometabolic parameters, multivariate Cox proportional hazard models were fitted for mediation analysis. Of 15,154 subjects with negative index endoscopy findings during health check-up, 11,686 subjects who underwent repeated endoscopy were included. During follow-up, 1,367 incident ERD events (11.7%) were observed. Without mediation effect, the multivariate adjusted hazard ratio of BMI was 1.21 (95% CI, 1.03-1.42) in overweight and 1.39 (95% CI, 1.19-1.62) in obese individuals compared to normal weight individuals. When the metabolic syndrome was included as a mediator, the hazard ratio became 1.19 (95% CI, 1.00-1.40) in overweight and 1.29 (95% CI, 1.10-1.52) in obese individuals. Both systolic blood pressure and triglyceride level were found to fully mediate the effect of BMI on ERD. Fasting glucose level was a partial mediator. The estimated percentage of total effect mediated by cardiometabolic risk factors was 35.4%. Cardiometabolic parameters partially or fully mediate the association between overweight and obesity and incident ERD.

(E)-3-(3,5-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (DPP23) is a synthetic polyphenol derivative that selectively induces apoptosis in cancer cells through the unfolded protein response pathway. In the present study, we evaluated the effect of DPP23 on tumour invasion and metastasis. Here, we show that DPP23 inhibited tumour necrosis factor alpha (TNFα)-induced motility, F-actin formation, and the invasive capability of MDA-MB-231 cells. DPP23 inhibited NF-κB-dependent MMP-9 expression at the transcriptional level. Akt is involved in the activation of IKK, an upstream regulator of NF-κB. DPP23 inhibited IKK and Akt, and knockdown of Akt2 significantly inhibited TNFα-induced IKK phosphorylation. We found that DPP23 bound to the catalytic domain of Akt2, as revealed by an in silico molecular docking analysis. These results suggest that DPP23 prevents TNFα-induced invasion of highly metastatic MDA-MB-231 breast cancer cells by inhibiting Akt-IKK-NF-κB axis-mediated MMP-9 gene expression. In addition, DPP23 attenuated experimental liver metastasis in a syngenic intrasplenic transplantation model using 4T1 mouse mammary carcinoma cells. Collectively, these results suggest that DPP23 could be used as a potential platform for the prevention of invasion and metastasis of early-stage breast cancer or as an adjuvant for chemo/radiotherapy.

Compressible and monolithic microporous polymers (MPs) are reported. MPs were prepared as monoliths via a Sonogashira-Hagihara coupling reaction of 1,3,5-triethynylbenzene (TEB) with the bis(bromothiophene) monomer (PBT-Br). The polymers were reversibly compressible, and were easily cut into any form using a knife. Microscopy studies on the MPs revealed that the polymers had tubular microstructures, resembling those often found in marine sponges. Under compression, elastic buckling of the tube bundles was observed using an optical microscope. MP-0.8, which was synthesized using a 0.8:1 molar ratio of PBT-Br to TEB, showed microporosity with a BET surface area as high as 463 m(2)g(-1). The polymer was very hydrophobic, with a water contact angle of 145° and absorbed 7-17 times its own weight of organic liquids. The absorbates were released by simple compression, allowing recyclable use of the polymer. MPs are potential precursors of structured carbon materials; for example, a partially graphitic material was obtained by pyrolysis of MP-0.8, which showed a similar tubular structure to that of MP-0.8.