Methanooceanicella nereidis gen. nov., sp. nov., the first oceanic Methanocellaceae methanogen, isolated from potential methane hydrate bearing area offshore southwestern Taiwan.

A novel mesophilic, hydrogenotrophic methanogen, strain CWC-04T, was obtained from a sediment sample extracted from a gravity core retrieved at station 22 within the KP-9 area off the southwestern coast of Taiwan during the ORIII-1368 cruise in 2009. Cells of strain CWC-04T were rod-shaped, 1.4-2.9 µm long by 0.5-0.6 µm wide, and occurred singly. Strain CWC-04Tutilized formate, H2/CO2, 2-propanol/CO2 or 2-butanol/CO2 as catabolic substrates. The optimal growth conditions were 42 °C, 0.17 M NaCl and pH 5.35. The genomic DNA G+C content calculated from the genome sequence of strain CWC-04T was 46.19 mol%. Phylogenetic analysis of 16S rRNA gene revealed that strain CWC-04T is affiliated with the genus Methanocella. The 16S rRNA gene sequences similarities within strains Methanocella arvoryzae MRE50T, Methanocella paludicola SANAET and Methanocella conradii HZ254T were 93.7, 93.0 and 91.3 %, respectively. In addition, the optical density of CWC-04T culture dropped abruptly upon entering the late-log growth phase, with virus-like particles (150 nm in diameter) being observed on and around the cells. This observation suggests that strain CWC-04T harbours a lytic virus. Based on these phenotypic, phylogenetic and genomic results, we propose that strain CWC-04T represents a novel species of a novel genus in the family Methanocellaceae, for which the name Methanooceanicella nereidis gen. nov., sp. nov. is proposed. The type strain is CWC-04T (=BCRC AR10050T=NBRC 113165T).

Methanovulcanius yangii gen. nov., sp. nov., a hydrogenotrophic methanogen, isolated from a submarine mud volcano in the offshore area of southwestern Taiwan.

A novel mesophilic, hydrogenotrophic methanogen, strain CYW5T, was isolated from a sediment sample of a piston core collected from submarine mud volcano MV5 located in the offshore area of southwestern Taiwan. Cells of strain CYW5T were irregular coccids, 0.5-1.0 µm in diameter and lysed easily by 0.01 % sodium dodecyl sulphate (SDS) treatment. Strain CYW5Tutilized formate or hydrogen plus carbon dioxide as catabolic substrates for methanogenesis. The optimal growth conditions were 37 °C, 0.043-0.085 M NaCl and pH 6.02-7.32. The genomic DNA G+C content calculated from the genome sequence of strain CYW5T was 56.2 mol%. The results of phylogenetic analysis of 16S rRNA gene sequences indicated that strain CYW5T represented a member of the family Methanomicrobiaceae in the order Methanomicrobiales, and was closely related to the members of the genus Methanogenium. The most closely related species was Methanogenium cariaci JR1T (94.9 % of 16S rRNA gene sequence identity). The average nucleotide identity and average amino acid identity values between strain CYW5T and members of the family Methanomicrobiaceae were 74.7-78.5 % and 49.1-64.9%, respectively. Although many of the morphological and physiological characteristics of strain CYW5T and the species of the genus Methanogenium were similar, they were distinguishable by the differences in genomic G+C content and temperature, NaCl and pH ranges for growth. Based on these phenotypic, phylogenetic and genomic results, we propose that strain CYW5T represents a novel species, of a novel genus, named Methanovulcanius yangii gen. nov., sp. nov. The type strain is CYW5T (=BCRC AR10048T=DSM 100756T=NBRC 111404T).

Protective Effect of Vaccine Doses and Antibody Titers Against SARS-CoV-2 Infection in Kidney Transplant Recipients.

Patients undergoing kidney transplantation have a poor response to vaccination and a higher risk of disease progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The effectiveness of vaccine doses and antibody titer tests against the mutant variant in these patients remains unclear. We retrospectively analyzed the risk of SARS-CoV-2 infection in a single medical center according to vaccine doses and immune responses before the outbreak. Among 622 kidney transplant patients, there were 77 patients without vaccination, 26 with one dose, 74 with two doses, 357 with three, and 88 with four doses. The vaccination status and infection rate proportion were similar to the general population. Patients undergoing more than three vaccinations had a lower risk of infection (odds ratio = 0.6527, 95% CI = 0.4324-0.9937) and hospitalization (odds ratio = 0.3161, 95% CI = 0.1311-0.7464). Antibody and cellular responses were measured in 181 patients after vaccination. Anti-spike protein antibody titer of more than 1,689.3 BAU/mL is protective against SARS-CoV-2 infection (odds ratio = 0.4136, 95% CI = 0.1800-0.9043). A cellular response by interferon-γ release assay was not correlated with the disease (odds ratio = 1.001, 95% CI = 0.9995-1.002). In conclusion, despite mutant strain, more than three doses of the first-generation vaccine and high antibody titers provided better protection against the omicron variant for a kidney transplant recipient.

Humeral and cellular immune responses to SARS-CoV-2 vaccination in patients on peritoneal dialysis.

BACKGROUND: Patients with chronic kidney disease are at high risk for coronavirus disease 2019. Little is known about immune response to severe acute respiratory syndrome coronavirus 2 vaccination in patients on peritoneal dialysis (PD). METHOD: We prospectively enrolled 306 PD patients receiving two doses of vaccines (ChAdOx1-S: 283, mRNA-1273: 23) from July 2021 at a medical center. Humeral and cellular immune responses were assessed by anti-spike IgG concentration and blood T cell interferon-γ production 30 days after vaccination. Antibody ≥0.8 U/mL and interferon-γ ≥ 100 mIU/mL were defined as positive. Antibody was also measured in 604 non-dialysis volunteers (ChAdOx1-S: 244, mRNA-1273: 360) for comparison. RESULT: PD patients had less adverse events after vaccinations than volunteers. After the first dose of vaccine, the median antibody concentrations were 8.5 U/mL and 50.4 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 66.6 U/mL and 195.3 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. And after the second dose of vaccine, the median antibody concentrations were 344.8 U/mL and 9941.0 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 620.3 U/mL and 3845.0 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. The median IFN-γ concentration was 182.8 mIU/mL in ChAdOx1-S group, which was substantially lower than the median concentration 476.8 mIU/mL in mRNA-1273 group of PD patients. CONCLUSION: Both vaccines were safe and resulted in comparable antibody seroconversion in PD patients when compared with volunteers. However, mRNA-1273 vaccine induced significantly higher antibody and T cell response than ChAdOx1-S in PD patients. Booster doses are recommended for PD patients after two doses of ChAdOx1-S vaccination.

Development of Innovative Online Modularized Device for Turbidity Monitoring.

Given progress in water-quality analytical technology and the emergence of the Internet of Things (IoT) in recent years, compact and durable automated water-quality monitoring devices have substantial market potential. Due to susceptibility to the influence of interfering substances, which lowers measurement accuracy, existing automated online monitoring devices for turbidity, a key indicator of a natural water body, feature a single light source and are thus insufficient for more complicated water-quality measurement. The newly developed modularized water-quality monitoring device boasts dual light sources (VIS/NIR), capable of measuring the intensity of scattering, transmission, and reference light at the same time. Coupled with a water-quality prediction model, it can attain a good estimate for continuing monitoring of tap water (<2 NTU, error < 0.16 NTU, relative error < 19.6%) and environmental water samples (<400 NTU, error < 3.86 NTU, relative error < 2.3%). This indicates the optical module can both monitor water quality in low turbidity and provide water-treatment information alerts in high turbidity, thereby materializing automated water-quality monitoring.

Predictors of chronic pain and disability in patients treated conservatively after distal radius fracture: a prospective cohort study.

PURPOSE: To determine predictors of chronic pain and disability among patients with distal radius fractures (DRF) treated conservatively with closed reduction and cast immobilization. METHODS: This was a prospective cohort study. Information on patient characteristics, post-reduction radiographic parameters, finger and wrist range of motion, psychological status (Hospital Anxiety and Depression Scale or HADS), pain (Numeric Rating Scale or NRS), and self-perceived disability (Disabilities of the Arm, Should, and Hand or DASH) were taken at baseline, cast removal, and 24 weeks. Differences in outcomes between time points were determined using analysis of variance. Multiple linear regressions were used to determine predictors of pain and disability at 24 weeks. RESULTS: One hundred forty patients with DRF (70% women, age: 67.0 ± 17.9) completed 24 weeks of follow-up and were included in the analysis. NRS (off-cast), range of ulnar deviation (off-cast), and greater occupational demands were significant predictors of pain at week 24 (adjusted R2 = 0.331, p < 0.001). Significant predictors of perceived disability at week 24 were HADS (off cast), sex (female), dominant-hand injury, and range of ulnar deviation (off cast) (adjusted R2 = 0.265, p < 0.001). CONCLUSIONS: Off-cast NRS and HADS scores are important modifiable predictors of patient-reported pain and disability at 24 weeks in patients with DRF. These factors should be targeted in the prevention of chronic pain and disability post-DRF.

Anticancer Study of a Novel Pan-HDAC Inhibitor MPT0G236 in Colorectal Cancer Cells.

Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies and a leading cause of cancer worldwide. Histone deacetylases (HDACs), which regulate cell proliferation and survival, are associated with the development and progression of cancer. Moreover, HDAC inhibitors are promising therapeutic targets, with five HDAC inhibitors approved for cancer treatment to date. However, their safety profile necessitates the exploration of well-tolerated HDAC inhibitors that can be used in cancer therapeutic strategies. In this study, the pan-HDAC inhibitor MPT0G236 reduced the viability and inhibited the proliferation of human colorectal cancer cells, and normal human umbilical vein endothelial cells (HUVECs) showed reduced sensitivity. These findings indicated that MPT0G236 specifically targeted malignant tumor cells. Notably, MPT0G236 significantly inhibited the activities of HDAC1, HDAC2, and HDAC3, Class I HDACs, as well as HDAC6, a Class IIb HDAC, at low nanomolar concentrations. Additionally, it promoted the accumulation of acetyl-α-tubulin and acetyl-histone H3 in HCT-116 and HT-29 cells in a concentration-dependent manner. Furthermore, MPT0G236 treatment induced G2/M cell cycle arrest in CRC cells by initially regulating the levels of cell-cycle-related proteins, such as p-MPM2; specifically reducing p-cdc2 (Y15), cyclin B1, and cdc25C levels; and subsequently inducing apoptosis through the caspase-dependent pathways and PARP activation. Our findings demonstrate that MPT0G236 exhibits significant anticancer activity in human colorectal cancer cells.

Children with Mycoplasma pneumoniae infection in Taiwan: Changes in molecular characteristics and clinical outcomes.

BACKGROUND: Mycoplasma pneumoniae is a pathogen that causes respiratory diseases in children. Infections caused by M. pneumoniae are usually self-limited but occasionally can be severe. We observed emerging cases of severe mycoplasma infection requiring extracorporeal membrane oxygenation (ECMO). Thus, we investigated chronological changes in the molecular features of the M. pneumoniae and its clinical impacts among the pediatric population. METHODS: From 2011 to 2019, respiratory samples were collected from patients younger than 18 years old with pneumonia in a tertiary children's hospital. Focused multiple-locus variable number of tandem repeats analysis (MLVA) typing was performed on samples positive for M. pneumoniae in 2016 and 2019. Clinical data from the patients' electronic medical records were collected. We described the annual trend of macrolide resistance and MLVA type and analyzed the associations between clinical manifestations and MLVA types. RESULTS: The percentage of macrolide-resistant (MLR) M. pneumoniae gradually increased from 22% (27/122) in 2015 to 70% (82/117) in 2019. Among the MLRM. pneumoniae, the predominant strain shifted from type P (31% [13/42]) to type A (40% [19/46]). The demographics, initial presentations, and clinical courses of the subjects with MLRM. pneumoniae did not differ significantly between 2011 and 2019. However, in 2019, two fulminant cases requiring venovenous ECMO were observed, which indicates that more attention to the clinical severity of MLRM. pneumoniae infections is warranted. CONCLUSION: Obtaining accurate information on macrolide susceptibility is crucial for physicians to initiate appropriate antibiotic treatment in a timely fashion. Although we could not identify significant differences among mycoplasma pneumonias caused by different MLVAs over a span of 9 years, the emergence of severe mycoplasma infections requiring ECMO was clinically significant, and further monitoring was required.

Clinical characteristics and outcomes of neonates with polymicrobial ventilator-associated pneumonia in the intensive care unit.

BACKGROUND: Ventilator associated pneumonia (VAP) caused by more than one microorganisms is not uncommon and may be potentially challenging, but the relevant data is scarce in ventilated neonates. We aimed to investigate the clinical characteristics and outcomes of polymicrobial VAP in the neonatal intensive care unit (NICU). METHODS: All neonates with definite diagnosis of VAP from a tertiary level neonatal intensive care unit (NICU) in Taiwan between October 2017 and September 2020 were prospectively observed and enrolled for analyses. All clinical features, therapeutic interventions and outcomes were compared between the polymicrobial VAP and monomicrobial VAP episodes. Multivariate regression analyses were used to find the independent risk factors for treatment failure. RESULTS: Among 236 episodes of neonatal VAP, 60 (25.4%) were caused by more than one microorganisms. Polymicrobial VAP episodes were more likely to be associated with multidrug-resistant pathogens (53.3% versus 34.7%, P = 0.014), more often occurred in later days of life and in neonates with prolonged intubation and underlying bronchopulmonary dysplasia. Otherwise most clinical characteristics of polymicrobial VAP were similar to those of monomicrobial VAP. The therapeutic responses and treatment outcomes were also comparable between these two groups, although modification of therapeutic antibiotics were significantly more common in polymicrobial VAP episodes than monomicrobial VAP episodes (63.3% versus 46.2%; P < 0.001). None of any specific pathogens was significantly associated with worse outcomes. Instead, it is the severity of illness, including presence of concurrent bacteremia, septic shock, and requirement of high-frequency oscillatory ventilator and underlying neurological sequelae that are independently associated with treatment failure. CONCLUSIONS: Polymicrobial VAP accounted for 25.4% of all neonatal VAP in the NICU, and frequently occurred in neonates with prolonged intubation and underlying bronchopulmonary dysplasia. In our cohort, most clinical features, therapeutic responses and final outcomes of neonates with monomicrobial and polymicrobial VAP did not differ significantly.

Effect of 3-subsitution of quinolinehydroxamic acids on selectivity of histone deacetylase isoforms.

A series of 3-subsituted quinolinehydroxamic acids has been synthesised and evaluated for their effect on human lung cancer cell line (A549), human colorectal cancer cell line (HCT116) and HDAC isoforms 1, 2, 6, and 8. The results indicated that substitution at C3 of quinoline is favoured for HDAC6 selectivity. Two compounds (25 and 26) were also found to be potent anti-proliferative compounds with IC50 values ranging from 1.29 to 2.13 µM against A549 and HCT116 cells. These compounds displayed remarkable selectivity for HDAC6 over other HDAC isoforms with nanomolar IC50 values. Western blot analysis revealed that compounds of this series activate apoptotic caspase pathway as indicated by cleavage of caspase 3, 8, and 9 and also increase phosphorylated H2AX thus inducing DNA double strand fragmentation in a concentration dependent manner. Flow cytometric analysis also displayed a dose dependent increase of cell population in sub G1 phase.

Clustered Regularly Interspaced Short Palindromic Repeat Analysis of Clonal Complex 17 Serotype III Group B Streptococcus Strains Causing Neonatal Invasive Diseases.

Group B Streptococcus (GBS) is an important pathogen of neonatal infections, and the clonal complex (CC)-17/serotype III GBS strain has emerged as the dominant strain. The clinical manifestations of CC17/III GBS sepsis may vary greatly but have not been well-investigated. A total of 103 CC17/III GBS isolates that caused neonatal invasive diseases were studied using a new approach based on clustered regularly interspaced short palindromic repeats (CRISPR) loci and restriction fragment length polymorphism (RFLP) analyses. All spacers of CRISPR loci were sequenced and analyzed with the clinical presentations. After CRISPR-RFLP analyses, a total of 11 different patterns were observed among the 103 CRISPR-positive GBS isolates. GBS isolates with the same RFLP patterns were found to have highly comparable spacer contents. Comparative sequence analysis of the CRISPR1 spacer content revealed that it is highly diverse and consistent with the dynamics of this system. A total of 29 of 43 (67.4%) spacers displayed homology to reported phage and plasmid DNA sequences. In addition, all CC17/III GBS isolates could be categorized into three subgroups based on the CRISPR-RFLP patterns and eBURST analysis. The CC17/III GBS isolates with a specific CRISPR-RFLP pattern were more significantly associated with occurrences of severe sepsis (57.1% vs. 29.3%, p = 0.012) and meningitis (50.0% vs. 20.8%, p = 0.009) than GBS isolates with RFLP lengths between 1000 and 1300 bp. Whole-genome sequencing was also performed to verify the differences between CC17/III GBS isolates with different CRISPR-RFLP patterns. We concluded that the CRISPR-RFLP analysis is potentially applicable to categorizing CC17/III GBS isolates, and a specific CRISPR-RFLP pattern could be used as a new biomarker to predict meningitis and illness severity after further verification.

The HDAC/HSP90 Inhibitor G570 Attenuated Blue Light-Induced Cell Migration in RPE Cells and Neovascularization in Mice through Decreased VEGF Production.

Age-related macular degeneration (AMD) occurs due to an abnormality of retinal pigment epithelium (RPE) cells that leads to gradual degeneration of the macula. Currently, AMD drug pipelines are endowed with limited options, and anti-VEGF agents stand as the dominantly employed therapy. Despite the proven efficacy of such agents, the evidenced side effects associated with their use underscore the need to elucidate other mechanisms involved and identify additional molecular targets for the sake of therapy improvement. The previous literature provided us with a solid rationale to preliminarily explore the potential of selective HDAC6 and HSP90 inhibitors to treat wet AMD. Rather than furnishing single-target agents (either HDAC6 or HSP90 inhibitor), this study recruited scaffolds endowed with the ability to concomitantly modulate both targets (HDAC6 and HSP90) for exploration. This plan was anticipated to accomplish the important goal of extracting amplified benefits via dual inhibition (HDAC6/HSP90) in wet AMD. As a result, G570 (indoline-based hydroxamate), a dual selective HDAC6-HSP90 inhibitor exerting its effects at micromolar concentrations, was pinpointed in the present endeavor to attenuate blue light-induced cell migration and retinal neovascularization by inhibiting VEGF production. In addition to the identification of a potential chemical tool (G570), the outcome of this study validates the candidate HDAC6-HSP90 as a compelling target for the development of futuristic therapeutics for wet AMD.

HDAC inhibitor protects chronic cerebral hypoperfusion and oxygen-glucose deprivation injuries via H3K14 and H4K5 acetylation-mediated BDNF expression.

Vascular dementia (VaD) is the second most common cause of dementia, but the treatment is still lacking. Although many studies have reported that histone deacetylase inhibitors (HDACis) confer protective effects against ischemic and hypoxic injuries, their role in VaD is still uncertain. Previous studies shown, one HDACi protected against cognitive decline in animals with chronic cerebral hypoperfusion (CCH). However, the underlying mechanisms remain elusive. In this study, we tested several 10,11-dihydro-5H-dibenzo[b,f]azepine hydroxamates, which act as HDACis in the CCH model (in vivo), and SH-SY5Y (neuroblastoma cells) with oxygen-glucose deprivation (OGD, in vitro). We identified a compound 13, which exhibited the best cell viability under OGD. The compound 13 could increase, in part, the protein levels of brain-derived neurotrophic factor (BDNF). It increased acetylation status on lysine 14 residue of histone 3 (H3K14) and lysine 5 of histone 4 (H4K5). We further clarified which promoters (I, II, III, IV or IX) could be affected by histone acetylation altered by compound 13. The results of chromatin immunoprecipitation and Q-PCR analysis indicate that an increase in H3K14 acetylation leads to an increase in the expression of BDNF promoter II, while an increase in H4K5 acetylation results in an increase in the activity of BDNF promoter II and III. Afterwards, these cause an increase in the expression of BDNF exon II, III and coding exon IX. In summary, the HDACi compound 13 may increase BDNF specific isoforms expression to rescue the ischemic and hypoxic injuries through changes of acetylation on histones.

Elevated plasma phage load as a marker for intestinal permeability in leukemic patients.

Microbial translocation (MT) and altered gut microbiota have been described in acute leukemic patients and contribute to immune activation and inflammation. However, phage translocation has not been investigated in leukemia patients yet. We recruited 44 leukemic patients and 52 healthy adults and quantified the levels of 3 phages in peripheral blood, which were the most positive phages screened from fecal samples. The content of 16S rRNA in plasma was detected by qPCR to assess the intestinal mucosa of these patients. Spearman's rank correlation was used to analyze the relationship between phage load and the relevant clinical data. We found the most prevalent phages in fecal samples were λ phage, Wphi phage, and P22 phage, and λ phage had the highest detection rate in plasma (68%). Phage content was affected by chemotherapy and course of disease and correlated with the levels of CRP (r = 0.43, p = 0.003), sCD14 (r = 0.37, p = 0.014), and sCD163 (r = 0.44, p = 0.003). Our data indicate that plasma phage load is a promising marker for gut barrier damage and that gut phage translocation correlates with monocyte/macrophage activation and systemic inflammatory response in leukemic patients.

Methanofollis fontis sp. nov., a methanogen isolated from marine sediment near a cold seep at Four-Way Closure Ridge offshore southwestern Taiwan.

A mesophilic, hydrogenotrophic methanogen, strain FWC-SCC2T, was isolated from deep-sea sediments collected by a real-time video multiple-corer at the C5-6 station near a cold seep at Four-Way Closure Ridge region during R/V Ocean Researcher III ORIII-1900 cruise in 2015. The cells were irregular cocci, non-motile and 0.8-1.2 µm in diameter. The methanogenic substrates utilized by strain FWC-SCC2T were formate or H2+CO2, but not acetate, methanol, ethanol or methylamines. Strain FWC-SCC2T was lysed in SDS (0.01 %, w/v). The M r of surface-layer protein was 116 400. The optimum growth conditions of strain FWC-SCC2T were 37 °C, 0.17 M NaCl and pH 6.7-7.0. The genomic DNA G+C content calculated from the genome sequence of strain FWC-SCC2T was 59.5 mol %. Phylogenetic analysis revealed that strain FWC-SCC2T was a member of the genus Methanofollis, and was most closely related to Methanofollis tationis Chile 9T (97.6 % similarity of 16S rRNA gene sequence) and shared 97.4, 95.9, 95.9 and 95.4 % with Methanofollis liminatans GKZPZT, Methanofollis formosanus ML15T, Methanofollis aquaemaris N2F9704T and Methanofollis ethanolicus HASUT, respectively. The genome relatedness values between strain FWC-SCC2T and M. tationis DSM 2702T were estimated by average nucleotide identity and digital DNA-DNA hybridization analyses and the results were 79.4 and 21.2 %, respectively. Based on the differences in physiological and biochemical properties, 16S rRNA gene phylogeny and genome relatedness presented here, it is suggested that strain FWC-SCC2T represents a novel species of the genus Methanofollis, and the name Methanofollis fontis sp. nov. is proposed. The type strain is FWC-SCC2T (=BCRC AR10052T=DSM 107935T= NBRC 113164T).

Methanolobus halotolerans sp. nov., isolated from the saline Lake Tus in Siberia.

A halotolerant, psychrotolerant and methylotrophic methanogen, strain SY-01T, was isolated from the saline Lake Tus in Siberia. Cells of strain SY-01T were non-motile, cocci and 0.8-1.0 µm in diameter. The only methanogenic substrate utilized by strain SY-01T was methanol. The temperature range of growth for strain SY-01T was from 4 to 40 °C and the optimal temperature for growth was 30 °C. The pH range of growth was from pH 7.2 to 9.0, with optimal growth at pH 8.0. The NaCl range of growth was 0-1.55 M with optimal growth at 0.51 M NaCl. The G+C content of the genome of strain SY-01T was 43.6 mol % as determined by genome sequencing. Phylogenetic analysis revealed that strain SY-01T was most closely related to Methanolobus zinderi SD1T (97.3 % 16S rRNA gene sequence similarity), and had 95.5-97.2 % similarities to other Methanolobus species with valid names. Genome relatedness between strain SY-01T and DSM 21339T was computed using average nucleotide identity and digital DNA-DNAhybridization, which yielded values of 79.7 and 21.7 %, respectively. Based on morphological, phenotypic, phylogenetic and genomic relatedness data presented here, it is evident that strain SY-01T represents a novel species of the genus Methanolobus, and the name Methanolobus halotolerans sp. nov. is proposed. The type strain is SY-01T (=BCRC AR10051T=NBRC 113166 T=DSM 107642T).

A Bibenzyl Component Moscatilin Mitigates Glycation-Mediated Damages in an SH-SY5Y Cell Model of Neurodegenerative Diseases through AMPK Activation and RAGE/NF-κB Pathway Suppression.

Moscatilin can protect rat pheochromocytoma cells against methylglyoxal-induced damage. Elimination of the effect of advanced glycation end-products (AGEs) but activation of AMP-activated protein kinase (AMPK) are the potential therapeutic targets for the neurodegenerative diseases. Our study aimed to clarify AMPK signaling's role in the beneficial effects of moscatilin on the diabetic/hyperglycemia-associated neurodegenerative disorders. AGEs-induced injury in SH-SY5Y cells was used as an in vitro neurodegenerative model. AGEs stimulation resulted in cellular viability loss and reactive oxygen species production, and mitochondrial membrane potential collapse. It was observed that the cleaved forms of caspase-9, caspase-3, and poly (ADP-ribose) polymerase increased in SH-SY5Y cells following AGEs exposure. AGEs decreased Bcl-2 but increased Bax and p53 expression and nuclear factor kappa-B activation in SH-SY5Y cells. AGEs also attenuated the phosphorylation level of AMPK. These AGEs-induced detrimental effects were ameliorated by moscatilin, which was similar to the actions of metformin. Compound C, an inhibitor of AMPK, abolished the beneficial effects of moscatilin on the regulation of SH-SY5Y cells' function, indicating the involvement of AMPK. In conclusion, moscatilin offers a promising therapeutic strategy to reduce the neurotoxicity or AMPK dysfunction of AGEs. It provides a potential beneficial effect with AGEs-related neurodegenerative diseases.

Differential circRNA expression profiles in latent human cytomegalovirus infection and validation using clinical samples.

Human cytomegalovirus (HCMV) is an opportunistic prototypic beta-herpesvirus that can cause severe and even fatal diseases in immune-naive newborns and immunocompromised adults. Host-virus interactions occurring at the transcriptional and posttranscriptional levels are critical for establishing an HCMV latent or lytic infection, but the mechanisms remain poorly understood. Herein, we investigated the expression of circRNAs in human leukemia monocytes (THP-1 cells) latently infected with HCMV and explored the diagnostic value of circRNAs in children with HCMV infection. A total of 2,110 and 1,912 circRNAs were identified in mock-infected and HCMV latent-infected THP-1 cells, respectively. Of these, we identified 1,421 differently expressed circRNAs, of which 650 were upregulated and 771 were downregulated. The host genes corresponding to the differentially expressed circRNAs were mainly involved in the regulation of host cell secretion pathways, cell cycle, and cell apoptosis. The differentially expressed circRNAs had binding sites for microRNAs, suggesting an important role in the mechanism of HCMV latent infection. Furthermore, a clinical analysis showed that the expression levels of hsa_circ_0001445 and hsa_circ_0001206 were statistically significantly different in HCMV-infected patients vs. normal controls, suggesting that these circRNAs could potentially serve as biomarkers of HCMV-infection.

Risk of Infective Endocarditis After Invasive Dental Treatments: Case-Only Study.

BACKGROUND: Invasive dental treatments (IDTs) can yield temporary bacteremia and have therefore been considered a potential risk factor of infective endocarditis (IE). It is hypothesized that, through the trauma caused by IDTs, bacteria gain entry to the bloodstream and may attach to abnormal heart valves or damaged heart tissue, giving rise to IE. However, the association between IDTs and IE remains controversial. The aim of this study is to estimate the association between IDTs and IE. METHODS: The data in this study were obtained from the Health Insurance Database in Taiwan. We selected 2 case-only study designs, case-crossover and self-controlled case series, to analyze the data. The advantage of these methods is that confounding factors that do not vary with time are adjusted for implicitly. In the case-crossover design, a conditional logistic regression model with exposure to IDTs was used to estimate the risks of IE following an IDT with 4, 8, 12, and 16 weeks delay, respectively. In the self-controlled case series design, a conditional Poisson regression model was used to estimate the risk of IE for the risk periods of 1 to 4, 5 to 8, 9 to 12, and 13 to 16 weeks following an IDT. RESULTS: In total, 9120 and 8181 patients with IE were included in case-crossover design and self-controlled case series design, respectively. In the case-crossover design, 277 cases and 249 controls received IDTs during the exposure period, and the odds ratio was 1.12 (95% confidence interval, 0.94-1.34) for 4 weeks. In the self-controlled case series design, we observed that 407 IEs occurred during the first 4 weeks after IDTs, and the age-adjusted incidence rate ratio was 1.14 (95% confidence interval, 1.02-1.26) for 1 to 4 weeks after IDTs. CONCLUSIONS: In both study designs, we did not observe a clinically larger risk for IE in the short periods after IDTs. We also found no association between IDTs and IE among patients with a high risk of IE. Therefore, antibiotic prophylaxis for the prevention of IE is not required for the Taiwanese population.

Accurate Classification of Diminutive Colorectal Polyps Using Computer-Aided Analysis.

BACKGROUND & AIMS: Narrow-band imaging is an image-enhanced form of endoscopy used to observed microstructures and capillaries of the mucosal epithelium which allows for real-time prediction of histologic features of colorectal polyps. However, narrow-band imaging expertise is required to differentiate hyperplastic from neoplastic polyps with high levels of accuracy. We developed and tested a system of computer-aided diagnosis with a deep neural network (DNN-CAD) to analyze narrow-band images of diminutive colorectal polyps. METHODS: We collected 1476 images of neoplastic polyps and 681 images of hyperplastic polyps, obtained from the picture archiving and communications system database in a tertiary hospital in Taiwan. Histologic findings from the polyps were also collected and used as the reference standard. The images and data were used to train the DNN. A test set of images (96 hyperplastic and 188 neoplastic polyps, smaller than 5 mm), obtained from patients who underwent colonoscopies from March 2017 through August 2017, was then used to test the diagnostic ability of the DNN-CAD vs endoscopists (2 expert and 4 novice), who were asked to classify the images of the test set as neoplastic or hyperplastic. Their classifications were compared with findings from histologic analysis. The primary outcome measures were diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic time. The accuracy, sensitivity, specificity, PPV, NPV, and diagnostic time were compared among DNN-CAD, the novice endoscopists, and the expert endoscopists. The study was designed to detect a difference of 10% in accuracy by a 2-sided McNemar test. RESULTS: In the test set, the DNN-CAD identified neoplastic or hyperplastic polyps with 96.3% sensitivity, 78.1% specificity, a PPV of 89.6%, and a NPV of 91.5%. Fewer than half of the novice endoscopists classified polyps with a NPV of 90% (their NPVs ranged from 73.9% to 84.0%). DNN-CAD classified polyps as neoplastic or hyperplastic in 0.45 ± 0.07 seconds-shorter than the time required by experts (1.54 ± 1.30 seconds) and nonexperts (1.77 ± 1.37 seconds) (both P < .001). DNN-CAD classified polyps with perfect intra-observer agreement (kappa score of 1). There was a low level of intra-observer and inter-observer agreement in classification among endoscopists. CONCLUSIONS: We developed a system called DNN-CAD to identify neoplastic or hyperplastic colorectal polyps less than 5 mm. The system classified polyps with a PPV of 89.6%, and a NPV of 91.5%, and in a shorter time than endoscopists. This deep-learning model has potential for not only endoscopic image recognition but for other forms of medical image analysis, including sonography, computed tomography, and magnetic resonance images.