Transgelin-2, a novel cancer stem cell-related biomarker, is a diagnostic and therapeutic target for biliary tract cancer.

BACKGROUND: Biliary tract cancer (BTC) is a relatively rare but aggressive gastrointestinal cancer with a high mortality rate. Cancer stem cell (CSC) populations play crucial roles in tumor biology and are responsible for the low response to anti-cancer treatment and the high recurrence rate. This study investigated the role of Transgelin-2 (TAGLN2), overexpressed in CSC in BTC cells, and analyzed its expression in patient tissues and serum to identify potential new targets for BTC. METHODS: TAGLN2 expression was suppressed by small-interfering or short hairpin RNAs, and its effects on tumor biology were assessed in several BTC cell lines. Furthermore, the effects of TAGLN2 silencing on gemcitabine-resistant BTC cells, differentially expressed genes, proteins, and sensitivity to therapeutics or radiation were assessed. TAGLN2 expression was also assessed using western blotting and immunohistochemistry in samples obtained from patients with BTC to validate its clinical application. RESULTS: Suppression of TAGLN2 in BTC cell lines decreased cell proliferation, migration, invasion, and tumor size, in addition to a reduction in CSC features, including clonogenicity, radioresistance, and chemoresistance. TAGLN2 was highly expressed in BTC tissues, especially in cancer-associated fibroblasts in the stroma. Patients with a low stromal immunohistochemical index had prolonged disease-free survival compared to those with a high stromal immunohistochemical index (11.5 vs. 7.4 months, P = 0.013). TAGLN2 expression was higher in the plasma of patients with BTC than that in those with benign diseases. TAGLN2 had a higher area under the curve (0.901) than CA19-9, a validated tumor biomarker (0.799; P < 0.001). CONCLUSION: TAGLN2 plays a critical role in promoting BTC cell growth and motility and is involved in regulating BTC stemness. Silencing TAGLN2 expression enhanced cell sensitivity to radiation and chemotherapeutic drugs. The expression of TAGLN2 in patient tissue and plasma suggests its potential to serve as a secretory biomarker for BTC. Overall, targeting TAGLN2 could be an appropriate therapeutic strategy against advanced cancer following chemotherapy failure.

Mechanistic insight into human androgen receptor-mediated endocrine disrupting potential of cyclic depsipeptide mycotoxin, beauvericin, and influencing environmental factors for its biosynthesis in Fusarium oxysporum KFCC 11363P on rice cereal.

In current study, Fusarium mycotoxin, beauvericin (BEA), has endocrine disrupting potential through suppressing the exogenous androgen receptor (AR)-mediated transcriptional activation. BEA was classified as an AR antagonist, with IC30 and IC50 values indicating that it suppressed AR dimerization in the cytosol. BEA suppress the translocation of cytosolic activated ARs to the nucleus via exogenous androgens. Furthermore, we investigated the impact of environmental conditions for BEA production on rice cereal using response surface methodology. The environmental factors affecting the production of BEA, namely temperature, initial moisture content, and growth time were optimized at 20.28 °C, 42.79 % (w/w), and 17.31 days, respectively. To the best of our knowledge, this is the first report showing that BEA has endocrine disrupting potential through suppressing translocation of cytosolic ARs to nucleus, and temperature, initial moisture content, and growth time are important influencing environmental factors for its biosynthesis in Fusarium strains on cereal.

Differential DNA methylation and metabolite profiling of Atlantic killifish (Fundulus heteroclitus) from the New Bedford Harbor Superfund site.

Atlantic killifish (Fundulus heteroclitus) is a valuable model in evolutionary toxicology to study how the interactions between genetic and environmental factors serve the adaptive ability of organisms to resist chemical pollution. Killifish populations inhabiting environmental toxicant-contaminated New Bedford Harbor (NBH) show phenotypes tolerant to polychlorinated biphenyls (PCBs) and differences at the transcriptional and genomic levels. However, limited research has explored epigenetic alterations and metabolic effects in NBH killifish. To identify the involvement of epigenetic and metabolic regulation in the adaptive response of killifish, we investigated tissue- and sex-specific differences in global DNA methylation and metabolomic profiles of NBH killifish populations, compared to sensitive populations from a non-polluted site, Scorton Creek (SC). The results revealed that liver-specific global DNA hypomethylation and differential metabolites were evident in fish from NBH compared with those from SC. The sex-specific differences were not greater than the tissue-specific differences. We demonstrated liver-specific enriched metabolic pathways (e.g., amino acid metabolic pathways converged into the urea cycle and glutathione metabolism), suggesting possible crosstalk between differential metabolites and DNA hypomethylation in the livers of NBH killifish. Additional investigation of methylated gene regions is necessary to understand the functional role of DNA hypomethylation in the regulation of enzyme-encoding genes associated with metabolic processes and physiological changes in NBH populations.

Stimulation of estrogen receptor-alpha by hydroxyanilide fungicide, fenhexamid promotes lipid accumulation in 3 T3-L1 adipocyte.

Fenhexamid are fungicides that act against plant pathogens by inhibiting sterol biosynthesis. Nonetheless, it can trigger endocrine disruption and promote breast cancer cell growth. In a recent study, we investigated the mechanism underlying the lipid accumulation induced by fenhexamid hydroxyanilide fungicides in 3 T3-L1 adipocytes. To examine the estrogen receptor alpha (ERα)-agonistic effect, ER transactivation assay using the ERα-HeLa-9903 cell line was applied, and fenhexamid-induced ERα agonist effect was confirmed. Further confirmation that ERα-dependent lipid accumulation occurred was provided by treating 3 T3-L1 adipocytes with Methyl-piperidino-pyrazole hydrate (MPP), an ERα-selective antagonist. Fenhexamid mimicked the actions of ERα agonists and impacted lipid metabolism, and its mechanism involves upregulation of the expression of transcription factors that facilitate adipogenesis and lipogenesis. Additionally, it stimulated the expression of peroxisome proliferator-activated receptor (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), fatty acid synthase (FAS), and sterol regulatory element-binding protein 1 (SREBP1) and significantly elevated the expression of fatty acid-binding protein 4 (FABP4). In contrast, in combination with an ERα-selective antagonist, fenhexamid suppressed the expression of adipogenic/lipogenic transcription factors. These results suggest that fenhexamid affects the endocrine system and leads to lipid accumulation by interfering with processes influenced by ERα activation.

Muricauda meishanensis sp. nov., a facultative anaerobic bacterium belonging to the family Flavobacteriaceae isolated from marine sediment in the East China Sea.

A facultative anaerobic, Gram-strain-negative, rod-shaped bacterium (strain NBU2970T) was isolated by using modified ichip in situ cultivation from a marine sediment sample collected from Meishan Island in the East China Sea. Strain NBU2970T grew optimally at 37 °C, with a NaCl concentration of 2.0 % (w/v) and at pH 7.0. The 16S rRNA gene sequence analyses revealed that strain NBU2970T represents a novel species with the genus Muricauda, sharing highest sequence identities with Muricauda beolgyonensis BB-My12T (96.1 %), Muricauda alvinocaridis SCR12T (96.0 %), Muricauda taeanensis 105T (96.0 %) and Muricauda ruestringensis B1T (95.6 %). Phylogenetic analyses also indicated that strain NBU2970T clustered with the genus Muricauda and was closely related to M. beolgyonensis BB-My12T and M. ruestringensis B1T. The draft genome sequence of strain NBU2970T was composed of six contigs with a size of 3.2 Mbp, containing 3045 protein-coding genes and 38 RNA genes. The DNA G+C content was 43.8 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain NBU2970T and related species of the genus Muricauda were well below the threshold limit for prokaryotic species delineation. The major cellular fatty acids were iso-C15 : 0, iso-C15 : 1 G and iso-C17 : 0 3-OH. The only respiratory quinone was MK-6. The major polar lipid was phosphatidylethanolamine. Based on its phenotypic, chemotaxonomic and genotypic data, strain NBU2970T is considered to be a representative of a novel species in the genus Muricauda, for which the name Muricauda meishanensis sp. nov. is proposed. The type strain is NBU2970T (=KCTC 82915T=MCCC 1K06394T).

Evaluation of acquired antithrombin deficiency in paediatric patients supported on extracorporeal membrane oxygenation.

AIMS: There remains a paucity of literature regarding best practice for antithrombin (AT) monitoring, dosing and dose-response in paediatric extracorporeal membrane oxygenation (ECMO) patients. METHODS: We conducted a retrospective cohort study at a quaternary care paediatric intensive care unit in all patients <18 years of age supported on ECMO from 1 June 2011 to 30 April 2020. Adverse events and outcomes were characterized for all ECMO runs. AT activity and replacement were characterized and compared between two clinical protocols. AT activities measured post- vs. pre-AT replacement were compared in order to characterize a dose-response relationship. RESULTS: The final cohort included 191 patients with 201 ECMO runs and 2028 AT activity measurements. The median AT activity was 65% (interquartile range [IQR], 51-82) and 879 (43.3%) measurements met the criteria of deficient. The overall median AT dose and increase in AT activity were 50.6 units/kg/dose (IQR, 39.5-67.2) and 23.5% (IQR, 9.8-36.0), respectively. In the protocol that restricted AT activity measurements to clinical scenarios concerning for heparin resistance, there was significantly higher dosing in conjunction with significantly fewer overall administrations. Approximately one third of AT activity remained deficient after repletion. There was no difference in mechanical complications, reasons for discontinuation of ECMO support, time on ECMO or survival between protocols. CONCLUSIONS: There was a high prevalence of AT deficiency in paediatric ECMO patients. An AT replacement protocol based on evaluating heparin resistance is associated with fewer AT administrations, with similar circuit and patient outcomes. Further data are needed to identify optimal dosing strategies.

View-independent gait events detection using CNN-transformer hybrid network.

Accurate gait detection is crucial in utilizing the ample health information embedded in it. Vision-based approaches for gait detection have emerged as an alternative to the exacting sensor-based approaches, but their application has been rather limited due to complicated feature engineering processes and heavy reliance on lateral views. Thus, this study aimed to find a simple vision-based approach that is view-independent and accurate. A total of 22 participants performed six different actions representing standard and peculiar gaits, and the videos acquired from these actions were used as the input of the deep learning networks. Four networks, including a 2D convolutional neural network and an attention-based deep learning network, were trained with standard gaits, and their detection performance for both standard and peculiar gaits was assessed using measures including F1-scores. While all networks achieved remarkable detection performance, the CNN-Transformer network achieved the best performance for both standard and peculiar gaits. Little deviation by the speed of actions or view angles was found. The study is expected to contribute to the wider application of vision-based approaches in gait detection and gait-based health monitoring both at home and in clinical settings.

Improving older adults' autobiographical memory through video-conferencing intervention during COVID-19.

BACKGROUND: Autobiographical memory (AM) is valuable not only as an indicator of mental health and cognitive function, but also as a target of therapeutic intervention for older adults. In the context of the COVID-19 pandemic, the demand for online psychosocial interventions and assessment services has sharply increased. Thus, the present study examined the effectiveness of videoconferencing AM (vAM) intervention using the Ecological Momentary Assessment (EMA) method in addition to the traditional paper-and-pencil assessment among samples of community dwelling older adults. METHODS: Twenty-seven older adults (aged 66-86 years) participated in a vAM intervention composed of 4 weekly 90-min sessions. The primary outcome was AM specificity, with secondary outcomes as depressive symptom and cognitive function, measured before and after the intervention. In addition, daily emotions were measured through EMA over 4 weeks of intervention. The EMA data were analyzed using a multilevel analysis. RESULTS: The results showed low dropout rates (7%) and high EMA response rates (85%). Autobiographical memory specificity increased (Cohen's d = 0.678), and the level of depression declined significantly (Cohen's d = 0.375) after the program. Additionally, measures assessing cognitive function, such as Seoul Verbal Learning Test and DSC (Digit Symbol Coding), showed significant improvements. The EMA results indicated a decrease in the intensity and proportion of negative emotions experienced during the program. CONCLUSIONS: This study is the first to utilize videoconferencing and EMA to deliver an AM intervention targeting older adults. The intervention was effective in improving mental health and cognitive function, including AM in older adults. Additionally, EMA was found to be a feasible tool for use in older adults.

A phase I/II study of ivaltinostat combined with gemcitabine and erlotinib in patients with untreated locally advanced or metastatic pancreatic adenocarcinoma.

This phase I/II study evaluated the safety and efficacy of a new histone deacetylase (HDAC) inhibitor, ivaltinostat, in combination with gemcitabine and erlotinib for advanced pancreatic ductal adenocarcinoma (PDAC). Patients diagnosed with unresectable, histologically confirmed PDAC who had not undergone previous therapy were eligible. Phase I had a 3 + 3 dose escalation design to determine the maximum tolerable dose (MTD) of ivaltinostat (intravenously on days 1, 8 and 15) with gemcitabine (1000 mg/m2 intravenously on days 1, 8 and 15) and erlotinib (100 mg/day, orally) for a 28-day cycle. In phase II, patients received a six-cycle treatment with the MTD of ivaltinostat determined in phase I. The primary endpoint was the objective response rate (ORR). Secondary endpoints included overall survival (OS), disease control rate (DCR) and progression-free survival (PFS). The MTD of ivaltinostat for the phase II trial was determined to be 250 mg/m2 . In phase II, 24 patients were enrolled. The median OS and PFS were 8.6 (95% confidence interval [CI]: 5.3-11.2) and 5.3 months (95% CI: 3.7-5.8). Of the 16 patients evaluated for response, ORR and DCR were 25.0% and 93.8% with a median OS/PFS of 10.8 (95% CI: 8.3-16.7)/5.8 (95% CI: 4.6-6.7) months. Correlative studies showed that mutation burden detected by cfDNA and specific blood markers such as TIMP1, pro-MMP10, PECAM1, proMMP-2 and IGFBP1 were associated with clinical outcomes. Although the result of a small study, a combination of ivaltinostat, gemcitabine and erlotinib appeared to be a potential treatment option for advanced PDAC.

Pelagibius marinus sp. nov., a novel bacterium isolated from marine sediment, and emended description of the genus Pelagibius.

A Gram-stain-negative, rod-shaped, motile and aerobic marine bacterium, designated strain NBU2595T, was isolated from marine sediment sampled on Meishan Island, located in the East China Sea. Strain NBU2595T grew at 10-40 °C (optimum, 37 °C), at NaCl concentration of 0-10.0 % (w/v; optimum, 0.5 %) and at pH 6.0-8.0 (optimum, pH 7.0). Catalase and oxidase activities and H2S production were positive. Methyl red reaction and hydrolysis of casein, starch and Tweens 20, 40, 60 and 80 were negative. The major cellular fatty acids were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), C18 : 1 2-OH and C18 : 0 3-OH. The sole respiratory quinone was ubiquinone 10. The major polar lipids were phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine and phosphatidylmonomethylethanolamine. Comparative analysis of 16S rRNA gene sequences showed highest similarity to Pelagibius litoralis CL-UU02T (97.9%), and low similarities (<92.9 %) to other species. Phylogenetic analyses indicated that strain NBU2595T clustered with the genus Pelagibius and was closely related to P. litoralis CL-UU02T. The average nucleotide identity and digital DNA-DNA hybridization values between strain NBU2595T and the related species of the genus Pelagibius were well below the thresholds for prokaryotic species delineation. The DNA G+C content was 66.5 mol%. Based on its phenotypic, chemotaxonomic and genotypic data, strain NBU2595T should be placed in the genus Pelagibius as representing a novel species, for which the name Pelagibius marinus sp. nov. is proposed. The type strain is NBU2595T (=MCCC 1K04773T=KCTC 82223T).

Endocrine disrupting potential of selected azole and organophosphorus pesticide products through suppressing the dimerization of human androgen receptor in genomic pathway.

Several pesticides widely used in agriculture have been considered to be endocrine disrupting chemicals through their binding affinities to estrogen or androgen receptors. This study was conducted to clarify the human androgen receptor (hAR)-mediated genomic endocrine disrupting mechanism of eight selected pesticide products by in vitro assay providing the Organization for Economic Co-operation and Development Test Guideline No. 458, 22Rv1/MMTV_GR-KO AR transcriptional activation assay and a homo-dimerization confirmation assay. None of the tested pesticide products showed an AR agonistic effect, whereas they were all determined to be AR antagonists at non-toxic concentrations. Also, the eight pesticide products were verified as true AR antagonists through a specificity control test. In the Bioluminescence Resonance Energy Transfer-based AR homo-dimerization confirmation assay, the eight pesticide products did not induce AR homo-dimerization. Additionally, western blotting revealed that none of the eight pesticide products induced AR translocation from the cytoplasm to the nucleus. In conclusion, we found for the first-time evidence to understand the AR-mediated endocrine disrupting mechanisms induced by selected azole and organophosphorus pesticide products.

Bone healing on serial plain radiographs occurs slowly but adequately after medial opening wedge high tibial osteotomy without bone graft.

PURPOSE: The purpose of this study was to prospectively investigate osteotomy gap filling rates on serial plain radiographs, and to evaluate whether alignment correction is maintained after medial opening wedge high tibial osteotomy (MOWHTO) using a locking plate without bone graft. METHODS: Between March 2014 and June 2017, MOWHTO was performed without bone graft regardless of gap size. Radiographs were taken preoperatively, postoperatively, at 1, 3, 6, 12, 18, and 24 months after surgery. Radiographic examinations included a weight bearing long-standing anteroposterior (AP) view of the whole lower extremity, as well as, the AP, lateral, and both oblique views of the knee. Bone healing was measured on the medial oblique view of the knee. The postoperative alignment correction and its maintenance were assessed using the three radiologic parameters of the weight-bearing line (WBL) ratio, the hip-knee-ankle angle (HKAA), and the medial proximal tibial angle (MPTA) on the weight-bearing long-standing AP view of the lower extremity. RESULTS: Fifty-two consecutive patients underwent MOWHTO, but three patients failed to follow-up for more than 24 months. A total of 49 patients were assessed in this study. The median opening gap height was 10.0 mm (IQR, 8.0-12.0; range, 7-20). On immediate post-operative radiographs, the mean gap filling was 31.4 ± 3.6%. After 1, 3, 6, 12, 18, and 24 months, the mean gap filling rates increased to 38.7 ± 4.4%, 51.4 ± 6.6%, 66.5 ± 5.1%, 84.8 ± 7.0%, 92.4 ± 5.6%, and 97.8 ± 2.3%, respectively. Statistical differences were observed between all the follow-up evaluations (P < 0.001). Statistical differences in the WBL ratio, HKAA, and MPTA were observed between preoperatively and 1 month after surgery (P < 0.001). The mean PTSA increased significantly from preoperatively to postoperatively (P < 0.001). However, no statistical differences were found between the post-operative follow-up radiographs performed for these four values. CONCLUSION: MOWHTO using a locking plate without bone graft achieved at least 90% bone healing and had no loss in correction at 2 years postoperatively. LEVEL OF EVIDENCE: III.

GLRX3, a novel cancer stem cell-related secretory biomarker of pancreatic ductal adenocarcinoma.

BACKGROUND: Cancer stem cells (CSCs) are implicated in carcinogenesis, cancer progression, and recurrence. Several biomarkers have been described for pancreatic ductal adenocarcinoma (PDAC) CSCs; however, their function and mechanism remain unclear. METHOD: In this study, secretome analysis was performed in pancreatic CSC-enriched spheres and control adherent cells for biomarker discovery. Glutaredoxin3 (GLRX3), a novel candidate upregulated in spheres, was evaluated for its function and clinical implication. RESULTS: PDAC CSC populations, cell lines, patient tissues, and blood samples demonstrated GLRX3 overexpression. In contrast, GLRX3 silencing decreased the in vitro proliferation, migration, clonogenicity, and sphere formation of cells. GLRX3 knockdown also reduced tumor formation and growth in vivo. GLRX3 was found to regulate Met/PI3K/AKT signaling and stemness-related molecules. ELISA results indicated GLRX3 overexpression in the serum of patients with PDAC compared to that in healthy controls. The sensitivity and specificity of GLRX3 for PDAC diagnosis were 80.0 and 100%, respectively. When GLRX3 and CA19-9 were combined, sensitivity was significantly increased to 98.3% compared to that with GLRX3 or CA19-9 alone. High GLRX3 expression was also associated with poor disease-free survival in patients receiving curative surgery. CONCLUSION: Overall, these results indicate GLRX3 as a novel diagnostic marker and therapeutic target for PDAC targeting CSCs.

Paraneptunicella aestuarii gen. nov., sp. nov., a member of the family Alteromonadaceae isolated from seawater in East China Sea.

An aerobic Gram-stain-negative, curved rod-shaped and non-spore-forming bacterial strain (NBU2194T) was isolated from seawater collected in an intertidal zone in Ningbo, Zhejiang Province, PR China. It was motile though a single polar flagellum and grew at 20-42 °C (optimum, 30 °C), in 0-2.0 % NaCl (0 %, w/v) and at pH 5.0-9.0 (pH 6.0-7.0). The sole respiratory quinone was ubiquinone-8. The major cellular fatty acids were C16 : 0, C16 : 1 ω7c and/or C16 : 1 ω6c. The polar lipids contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, one unidentified phospholipid and two unidentified aminophosphoglycolipids. A phylogenetic analysis based on 16S rRNA gene sequences and 65 genomic core genes showed that strain NBU2194T formed a distinct lineage in the family Alteromonadaceae. The genome of strain NBU2194T was 4 913 533 bp with a DNA G+C content of 43.9 mol% and coded 3895 genes, 12 rRNA genes and 47 tRNA genes. The average nucleotide identity, amino acid identity and digital DNA-DNA hybridization values between strain NBU2194T and related species of Alteromonadaceae were below the threshold limit for prokaryotic species delineation. NBU2194T could be distinguished from other genera in the family Alteromonadaceae based on phenotypic, chemotaxonomic and genomic characteristics. On the basis of the polyphasic taxonomic evidence collected in this study, strain NBU2194T is considered to represent a novel genus and species in the family Alteromonadaceae, for which the name Paraneptunicella aestuarii is proposed. The type strain is NBU2194T (=KCTC 82442T=GDMCC 1.2217T).

Nisaea sediminum sp. nov., a heavy metal resistant bacterium isolated from marine sediment in the East China Sea.

A Gram-negative, rod-shaped, motile and strictly aerobic bacterium, designated NBU1469T, was isolated from marine sediment sampled on Meishan Island located in the East China Sea. Strain NBU1469T grew optimally at temperature of 40 °C, NaCl concentration of 2.0% (w/v) and pH 7.5. Catalase and oxidase activities, H2S production, nitrate reduction and hydrolysis of Tween 20 were positive. Indole, methyl red reaction, urease, hydrolysis of gelatin, starch, casein, Tweens 40, 60 and 80 were negative. The major cellular fatty acids were C16:0, C19:0 cyclo ω8c and summed feature 8 (C18:1 ω7c and/or C18:1 ω6c). The only respiratory quinone was ubiquinone-10 (Q-10). The major polar lipids were phosphatidylglycerol, two unidentified amino-phospholipids and two unidentified phospholipids. Comparative analysis of the 16S rRNA gene sequence showed highest similarities to the species with validated name Nisaea nitritireducens DR41_18T (98.1%) and Nisaea denitrificans DR41_21T (97.6%). Phylogenetic analyses indicated that strain NBU1469T formed a distinct lineage with strains Nisaea nitritireducens DR41_18T and Nisaea denitrificans DR41_21T within the genus Nisaea. The average nucleotide identity and digital DNA-DNA hybridization values between strain NBU1469T and related species of genus Nisaea were well below the threshold limit for prokaryotic species delineation. The DNA G + C content was 63.6%. Based on its phenotypic, chemotaxonomic and genotypic data, strain NBU1469T is considered to be a representative of a novel species in the genus Nisaea, for which the name Nisaea sediminum sp. nov. is proposed. The type strain is NBU1469T (=KCTC 82224 T =MCCC 1K04763T).

Microbulbifer hainanensis sp. nov., a moderately halopilic bacterium isolated from mangrove sediment.

A new bacterium was successfully isolated from a mangrove sediment sample in Haikou City, Hainan Province, China. The organism is a Gram-negative, rod-shaped, non-motile and strictly aerobic bacterium, named NBU-8HK146T. Strain NBU-8HK146T was able to grow at temperatures of 10-40 °C, at salinities of 0-11% (w/v) and at pH 5.5-9.5. Veoges-Proskauer, methyl red reaction and hydrolysis of Tween 20 were negative. Catalase and oxidase activities, H2S production, hydrolysis of starch, casein, Tweens 40, 60 and 80 were positive. The major cellular fatty acids were C16:0, iso-C15:0 and summed feature 9. The major respiratory quinone was ubiquinone-8 (Q-8). The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and two unidentified glycolipids. According to 16S rRNA gene sequence similarities, strain NBU-8HK146T shared 98.0%, 97.9%, 97.7%, 97.6% and 97.3% similarities to the species with validated name Microbulbifer taiwanensis CC-LN1-12T, Microbulbifer rhizosphaerae Cs16bT, Microbulbifer marinus Y215T, Microbulbifer donghaiensis CN85T and Microbulbifer aggregans CCB-MM1T, respectively. Phylogenetic analyses indicated that strain NBU-8HK146T formed a distinct lineage with strains Microbulbifer taiwanensis CC-LN1-12T and Microbulbifer marinus Y215T. Both digital DNA-DNA hybridization values (19.5-22.7%) and average nucleotide identity values (73.2-78.9%) between strain NBU-8HK146T and related species of genus Microbulbifer were below the species delineation cutoffs. The DNA G+C content was 58.9 mol%. Many proteins involving in the adaption of osmotic stress in the salt environment of mangrove were predicted in genome of strain NBU-8HK146T. From phenotypic, genotypic, phylogenetic and chemotaxonomic characteristics, strain NBU-8HK146T can be regarded as a new Microbulbifer species for which the name Microbulbifer hainanensis. The type strain is NBU-8HK146T (= KCTC 82226T = MCCC 1K04737T).

Relationship between allergic rhinitis and nasal surgery success in patients with obstructive sleep apnea.

OBJECTIVES: Nasal obstruction is common in patients with obstructive sleep apnea (OSA). Nonetheless, the effectiveness of isolated nasal surgery in treatment of OSA remains controversial. This study is to evaluate the subjective and objective outcome after isolated nasal surgery in patients with OSA and to determine the associated factors related to the success rate of isolated nasal surgery. METHODS: The study population consisted of 35 patients with nasal obstruction who had been diagnosed with OSA and were undergoing septoplasty and inferior turbinate reduction to correct nasal pathologies. Preoperative drug-induced sleep endoscopy was performed to evaluate the obstruction site. Patients were assessed before and after nasal surgery using subjective outcomes measures, including the Visual Analog Scale and Epworth Sleepiness Scale, as well as by overnight polysomnography. RESULTS: All patients experienced improved nasal breathing postoperatively. At 6 months postoperatively, patients exhibited significant symptomatic improvement in snoring, sleep apnea, morning headache, tiredness, and daytime sleepiness. Postoperative polysomnography revealed significant improvement in the apnea-hypopnea index, respiratory disturbance index, and percentage of time with oxygen saturation < 90%. Although the overall success rate of nasal surgery alone was 14.3%, the criteria for success were met in 50% of patients with allergic rhinitis. Furthermore, the success rate was significantly higher in patients with moderate to severe nasal obstruction than in patients with mild nasal obstruction. CONCLUSION: Among patients with OSA, those with allergic rhinitis and severe nasal obstruction are likely to have a better surgical outcome following isolated nasal surgery.

Identification of Circulating Serum miRNAs as Novel Biomarkers in Pancreatic Cancer Using a Penalized Algorithm.

Pancreatic cancer (PC) is difficult to detect in the early stages; thus, identifying specific and sensitive biomarkers for PC diagnosis is crucial, especially in the case of early-stage tumors. Circulating microRNAs are promising non-invasive biomarkers. Therefore, we aimed to identify non-invasive miRNA biomarkers and build a model for PC diagnosis. For the training model, blood serum samples from 63 PC patients and 63 control subjects were used. We selected 39 miRNA markers using a smoothly clipped absolute deviation-based penalized support vector machine and built a PC diagnosis model. From the double cross-validation, the average test AUC was 0.98. We validated the diagnosis model using independent samples from 25 PC patients and 81 patients with intrahepatic cholangiocarcinoma (ICC) and compared the results with those obtained from the diagnosis using carbohydrate antigen 19-9. For the markers miR-155-5p, miR-4284, miR-346, miR-7145-5p, miR-5100, miR-661, miR-22-3p, miR-4486, let-7b-5p, and miR-4703-5p, we conducted quantitative reverse transcription PCR using samples from 17 independent PC patients, 8 ICC patients, and 8 healthy individuals. Differential expression was observed in samples from PC patients. The diagnosis model based on the identified markers showed high sensitivity and specificity for PC detection and is potentially useful for early PC diagnosis.

Deep Generative Models-Based Anomaly Detection for Spacecraft Control Systems.

A spacecraft attitude control system provides mechanical and electrical control to achieve the required functions under various mission scenarios. Although generally designed to be highly reliable, mission failure can occur if anomalies occur and the attitude control system fails to properly orient and stabilize the spacecraft. Because accessing spacecraft to directly repair such problems is usually infeasible, developing a continuous condition monitoring model is necessary to detect anomalies and respond accordingly. In this study, a method for detecting anomalies and characterizing failures for spacecraft attitude control systems is proposed. Herein, features are extracted from multidimensional time-series data of a simulation of the attitude control system. Then, the artificial neural network learning algorithms based on two types of generation models are applied. A Bayesian optimization algorithm with a Gaussian process is used to optimize the hyperparameters for the neural network to improve the performance. The performance is evaluated based on the reconstruction error through the algorithm using the newly generated data not used for learning as input data. Results show that the detection performance depends on the operating characteristics of each submode in the operation scenarios and type of generation model. The diagnostic results are monitored to detect anomalies in operation modes and scenarios.

A novel indirubin derivative that increases somatic cell plasticity and inhibits tumorigenicity.

Indirubin-based compounds affect diverse biological processes, such as inflammation and angiogenesis. In this study, we tested a novel indirubin derivative, LDD-1819 (2-((((2Z,3E)-5-hydroxy-5'-nitro-2'-oxo-[2,3'-biindolinylidene]-3-ylidene)amino)oxy)ethan-1-aminium chloride) for two major biological activities: cell plasticity and anti-cancer activity. Biological assays indicated that LDD-1819 induced somatic cell plasticity. LDD-1819 potentiated myoblast reprogramming into osteogenic cells and fibroblast reprogramming into adipogenic cells. Interestingly, in an assay of skeletal muscle dedifferentiation, LDD-1819 induced human muscle cellularization and blocked residual proliferative activity to produce a population of mononuclear refractory cells, which is also observed in the early stages of limb regeneration in urodele amphibians. In cancer cell lines, LDD-1819 treatment inhibited cell invasion and selectively induced apoptosis compared to normal cells. In an animal tumor xenograft model, LDD-1819 reduced human cancer cell metastasis in vivo at doses that did not produce toxicity. Biochemical assays showed that LDD-1819 possessed inhibitory activity against glycogen synthase kinase-3ß, which is linked to cell plasticity, and aurora kinase, which regulates carcinogenesis. These results indicate that novel indirubin derivative LDD-1819 is a dual inhibitor of glycogen synthase kinase-3ß and aurora A kinase, and has potential for development as an anti-cancer drug or as a reprogramming agent for cell-therapy based approaches to treat degenerative diseases.