Optical design and performance of the biological small-angle X-ray scattering beamline at the Taiwan Photon Source.

The optical design and performance of the recently opened 13A biological small-angle X-ray scattering (SAXS) beamline at the 3.0 GeV Taiwan Photon Source of the National Synchrotron Radiation Research Center are reported. The beamline is designed for studies of biological structures and kinetics in a wide range of length and time scales, from angstrom to micrometre and from microsecond to minutes. A 4 m IU24 undulator of the beamline provides high-flux X-rays in the energy range 4.0-23.0 keV. MoB4C double-multilayer and Si(111) double-crystal monochromators (DMM/DCM) are combined on the same rotating platform for a smooth rotation transition from a high-flux beam of ∼4 × 1014 photons s-1 to a high-energy-resolution beam of ΔE/E ≃ 1.5 × 10-4; both modes share a constant beam exit. With a set of Kirkpatrick-Baez (KB) mirrors, the X-ray beam is focused to the farthest SAXS detector position, 52 m from the source. A downstream four-bounce crystal collimator, comprising two sets of Si(311) double crystals arranged in a dispersive configuration, optionally collimate the DCM (vertically diffracted) beam in the horizontal direction for ultra-SAXS with a minimum scattering vector q down to 0.0004 Å-1, which allows resolving ordered d-spacing up to 1 µm. A microbeam, of 10-50 µm beam size, is tailored by a combined set of high-heat-load slits followed by micrometre-precision slits situated at the front-end 15.5 m position. The second set of KB mirrors then focus the beam to the 40 m sample position, with a demagnification ratio of ∼1.5. A detecting system comprising two in-vacuum X-ray pixel detectors is installed to perform synchronized small- and wide-angle X-ray scattering data collections. The observed beamline performance proves the feasibility of having compound features of high flux, microbeam and ultra-SAXS in one beamline.

Pithecellobium clypearia extract enriched in gallic acid and luteolin has antibacterial activity against MRSA and reduces resistance to erythromycin, ceftriaxone sodium and levofloxacin.

AIMS: Antibiotic adjuvants can give a second life to the antibiotics to which bacteria are highly resistant. We evaluated the antimicrobial effects of extracts from Pithecellobium clypearia against methicillin-resistant Staphylococcus aureus (MRSA) and also the potential for synergy with several antibiotics. METHODS AND RESULTS: For this study, four extracts from P. clypearia were tested on MRSA using the broth microdilution method for activity assessment. The ethyl acetate fraction (S20b) had the strongest antibacterial activity against MRSA among the fractions tested. In all, 14 compounds such as gallic acid and luteolin in S20b were analysed by UFLC-Q-TOF-MS/MS. S20b combined with erythromycin showed synergy effects against MRSA and combined with ceftriaxone sodium and levofloxacin showed additive effects against MRSA. Electron microscopy showed that extract S20b damaged the MRSA cell wall and K+ efflux measurements indicated that extract S20b increased cell membrane permeability. Moreover, S20b suppression of PBP2a expression was assessed by Western blot. Furthermore, an in vivo study was used to investigate the therapeutic potential of S20b based on a mouse pneumonia model. CONCLUSIONS: The in vitro study results have shown that S20b not only inhibits MRSA growth directly but also reduces the resistance of MRSA to the evaluated antibacterial agents. Based on the in vivo study, it can be concluded that S20b can treat pneumonia in the mouse model. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first research to demonstrate that S20b can inhibit MRSA growth and reduce drug resistance of clinical isolates to antibiotics. S20b has the potential to be used as a therapeutic agent against MRSA and treatment for MRSA pneumonia.

[Analysis of pathogen spectrum and antimicrobial resistance of pathogens associated with hospital-acquired infections collected from 11 teaching hospitals in 2018].

Objective: To investigate the spectrum and antimicrobial resistance of major pathogens causing nosocomial infections in China, 2018. Methods: Non-duplicated nosocomial cases as well as pathogens causing bloodstream infections (BSI), hospital-acquired pneumonia (HAP) and intra-abdominal infections (IAI) from 11 teaching hospitals across China were collected. The minimum inhibitory concentrations (MICs) of clinically significant strains were determined by agar dilution method or broth microdilution method. The Clinical and Laboratory Standards Institute (CLSI) M100-S29 criteria were used for interpretation, and the WHONET-5.6 software was used in data analysis. Results: A total of 1 590 cases were collected, including 831 cases from BSI, 450 cases from HAP and 309 cases from IAI. The most prevalent pathogens causing BSI were Escherichia coli (29.2%, 243/831), Klebsiella pneumoniae (16.2%, 135/831) and Staphylococcus aureus (10.1%, 84/831); the most prevalent pathogens causing IAI were E. coli (26.2%, 81/309), Enterococcus faecium (15.5%, 48/309) and K. pneumoniae (13.3%, 41/309); while Acinetobacter baumanii (24.7%, 111/450), Pseudomonas aeruginosa (20.7%, 93/450) and K. pneumoniae (16.2%, 73/450) were dominated in HAP. All S. aureus were susceptible to tigecycline, linezolid, daptomycin and glycopeptides; 77.8% (105/135) of S. aureus strains were susceptible to ceftaroline. Methicillin-resistant S. aureus (MRSA) accounted for 29.6% (40/135) of all the S. aureus, and was lower than the accounted rate of methicillin-resistant coagulase-negative Staphylococcus (MRCNS) (83.7%, 41/49). One E. faecium strain (1.1%, 1/95) resistant to vacomycin and teicoplanin and one E. faecalis strain (2.3%, 1/43) resistant to linezolid was found. The prevalence of extended-spectrum ß-lactamase (ESBL) was 56.1% (193/344) in E. coli and 22.1% (55/249) in K. pneumonia; the rate of carbapenem resistant E. coli and K. pneumonia was 4.1% (14/344) and 22.9% (57/249), respectively; the percentage of ceftazidime/avibactam resistant E. coli and K. pneumonia was 2.3% (8/344) and 2.0% (5/249), respectively; the percentage of colistin resistant E. coli and K. pneumonia was 1.5% (5/344) and 7.6% (19/249), respectively; no E. coli and K. pneumonia strains were found resistant to tigecycline. The rate of carbapenem resistant A. baumanii and P. aeruginosa were 78.9% (146/185) and 36.7% (66/180), respectively. A. baumanii showed low susceptibility to the antimicrobial agents except colistin (99.5%, 184/185) and tigecycline (91.4%, 169/185). Colistin, amikacin and ceftazidime/avibactam demonstrated high antibacterial activity against P. aeruginosa with susceptility rate of 100% (180/180), 93.3% (168/180) and 85.6% (154/180), respectively. Conclusions: Nosocomial Gram-negative pathogens show high susceptibilities to tigecycline, colistin and ceftazidime/avibactam in vitro. Antimicrobial resistance in A. baumannii is a serious problem. The prevalence of carbapenem-resistant Enterobacteriaceae has increased, which should be monitored continuously in China.

Analysis of Damage and Wound Healing in the Retinal Pigmented Epithelium.

Previous studies of retinal pigment epithelium (RPE) morphology found cell-level and spatial patterning differences in many quantitative metrics in comparing normal and disease conditions. However, most of these studies examined eyes from deceased animals. Here we sought to compare noninvasively imaged RPE cells from live mice to histopathology. We describe changes to improve noninvasive imaging of RPE in the live mouse. In retinal diseases, there can be invasion by Iba1-positive cells, which can be detected by noninvasive imaging techniques. Here we can detect potential Iba1-positive cells at the level of the RPE noninvasively.

Saccharomyces cerevisiae Hog1 MAP kinase pathway is activated in response to honokiol exposure.

AIM: The goal of the study was to investigate the cellular tolerance mechanism in response to honokiol exposure. METHODS AND RESULTS: The broth microdilution method was employed to test the sensitivity of different Saccharomyces cerevisiae strains to honokiol. Intracellular levels of reactive oxygen species (ROSs) were determined by DCFH-DA staining. The phosphorylation of Hog1 was evaluated by Western blot analysis. The mRNA expressions of genes involved in the Ras-cyclic AMP (cAMP) pathway were analysed by real-time reverse transcription polymerase chain reaction. We found that the sod1▵ mutant was hypersensitive to honokiol and produced more ROS compared with wild-type and sod2▵ cells. Hog1 was phosphorylated in response to honokiol exposure and deletion of HOG1 increased the sensitivity to honokiol. The expressions of genes involved in the Ras-cAMP pathway were down-regulated after honokiol exposure; exogenous cAMP significantly reduced the phosphorylation of Hog1, although the level was higher than the control level. CONCLUSIONS: In addition to SOD1, the Ras-cAMP cascade and Hog1 MAP kinase pathway is essential for protecting against honokiol-induced oxidative stress. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results provide insight into the understanding of the action mechanism of honokiol.

Free-breathing coronary CT angiography using 16-cm wide-detector for challenging patients: comparison with invasive coronary angiography.

AIM: To investigate the superiority of free-breathing coronary computed tomography angiography (CCTA) with 16-cm wide-detector CT for challenging patients who cannot hold their breath. MATEIALS AND METHODS: A total of 76 patients (62% with either heart rate >75 beats/min or arrhythmia) who were unable to breath-hold underwent both free-breathing CCTA and invasive coronary angiography (ICA) were included. Two reviewers evaluated coronary arteries on a per-segment, per-vessel, and per-patient basis for image quality using a four-point scale and stenosis degree. CCTA results were compared with ICA to calculate the diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: Out of 1,368 segments, 228 (16.7%) were <1.5 mm in diameter and were excluded. Thirty-two (2.3%) with calcification and 26 (1.9%) with motion artefacts were considered positive at CT. One thousand and eighty-two segments (79.1%) were evaluated both on CCTA and ICA, and 128 (11.8%) segments had ≥50% stenosis on ICA. The diagnostic accuracy, sensitivity, specificity, PPV, and NPV of CCTA were 90.8%, 88.3%, 91.1%, 57.1%, and 98.3% on a per-segment basis; 93.4%, 90.6%, 94.2%, 80.5% and 97.4% on a per-vessel basis; and 92.1%, 100%, 85%, 85.7% and 100% on a per-patient basis. For patients with high heart rates or arrhythmia, 81% (versus 79.1%) segments were evaluable, and the accuracy, sensitivity, specificity, PPV, and NPV were statistically the same as the entire study population. CONCLUSION: Free-breathing CCTA using 16-cm wide-detector CT has high accuracy compared to ICA for detecting coronary artery stenosis for challenging patients.

Meta-analysis of cardiovascular toxicity risks in cancer patients on selected targeted agents.

PURPOSE: The purpose was to estimate the risk and severity of cardiovascular toxicities associated with selected targeted agents. METHODS: We searched English-language literature for randomized clinical trials published between January 1, 2000 and November 30, 2013 of targeted cancer therapy drugs approved by the FDA by November 2010. One hundred ten studies were eligible. Using meta-analytic methods, we calculated the relative risks of several cardiovascular toxicities [congestive heart failure (CHF), decreased left ventricular ejection fraction (DLVEF), myocardial infarction (MI), arrhythmia, and hypertension (HTN)], adjusting for sample size using the inverse-variance technique. For each targeted agent and side effect, we calculated the number needed to harm. RESULTS: Regarding CHF, trastuzumab showed significantly greater risk of all-grade and high-grade CHF. There was significant increased risk of all-grade DLVEF with sorafenib, sunitinib, and trastuzumab and high-grade DLVEF with bevacizumab and trastuzumab. Sorafenib was associated with significant increased all-grade risk of MI based on one study. None was associated with high-grade risk of MI or increased risk of arrhythmia. Bevacizumab, sorafenib, and sunitinib had significant increased risk of all-grade and high-grade HTN. CONCLUSIONS: Several of the targeted agents were significantly associated with increased risk of specific cardiovascular toxicities, CHF, DLVEF, and HTN. Several had significant increased risk for high-grade cardiovascular toxicities (CHF, DLVEF, and HTN). Patients receiving such therapy should be closely monitored for these toxicities and early and aggressive treatment should occur. However, clinical experience has demonstrated that some of these toxicities may be reversible and due to secondary effects.

Development of expressed sequence tag-based microsatellite markers for the critically endangered Isoëtes sinensis (Isoetaceae) based on transcriptome analysis.

Isoëtes sinensis is a critically endangered quillwort. To facilitate studies on the conservation genetics of this species, we developed expressed sequence tag-simple sequence repeat (EST-SSR) markers. A total of 50,063 unigenes were predicted by transcriptome sequencing, 5294 (10.6%) of which significantly matched 3011 Gene Ontology annotations and 2363 were assigned to Kyoto Encyclopedia of Genes and Genomes metabolic pathways. Most of these (2297) were involved in metabolism. A total of 1982 SSR motifs were identified, with trinucleotides being the dominant repeat motif, and 1438 (72.6%) SSR primers were designed. Eighteen randomly selected primer pairs were used to genotype 24 I. sinensis accessions, which confirmed the suitability of these novel markers for molecular studies of I. sinensis. The heterozygosity index value ranged between 0.0799 and 0.9106, while the Shannon-Wiener diversity index value ranged between 0.1732 and 2.5589. The EST-SSRs reported in this study are linked to genic sequences, and are therefore ideal for investigating the evolutionary history of I. sinensis. These markers, together with the large EST dataset generated in this study, will greatly facilitate conservation genetic studies of I. sinensis.

Development and characterization of microsatellite loci in Brasenia schreberi (Cabombaceae) based on the next-generation sequencing.

To understand genetic variability of the endangered aquatic herb Brasenia schreberi (Cabombaceae), we describe 31 microsatellite markers obtained using next-generation sequencing. A total of 24 individuals from the population of Jackson Lake, USA, were genotyped for each marker. Twenty-eight markers were polymorphic. The number of alleles per locus ranged from 1 to 9; the observed and expected heterozygosities ranged from 0 to 1 and from 0 to 0.751, respectively. These markers should be useful tools for genetic variation and conservation studies of B. schreberi.

Development of EST-SSR markers in the relict tree Davidia involucrata (Davidiaceae) using transcriptome sequencing.

Davidia involucrata, reputed to be a "living fossil" in the plant kingdom, is a relict tree endemic to China. Extant natural populations are diminishing due to anthropogenic disturbance. In order to understand its ability to survive in a range of climatic conditions and to design conservation strategies for this endangered species, we developed genic simple sequence repeats (SSRs) from mRNA transcripts. In total, 142,950 contigs were assembled. Of these, 30,411 genic SSR loci were discovered and 12,208 primer pairs were designed. Dinucleotides were the most common (77.31%) followed by trinucleotides (16.44%). Thirteen randomly selected primers were synthesized and validated using 24 individuals of D. involucrata. The markers displayed high polymorphism with the number of alleles per locus ranging from 3 to 12 and the observed and expected heterozygosities ranging from 0.083 to 1.0 and 0.102 to 0.69, respectively. This large expressed sequence tag dataset and the novel SSR markers will be key tools in comparative studies that may reveal the adaptive evolution, population structure, and resolve the genetic diversity in this endangered species.

[The effect of phospholipid transfer protein on cigarette smoke extract induced epithelial-mesenchymal transition of rat alveolar type â ¡ cells].

OBJECTIVE: To investigate the effect of phospholipid transfer protein(PLTP) on cigarette smoke extract(CSE) induced epithelial-mesenchymal transition(EMT) in rat alveolar Type Ⅱ cells (RLE-6TN). METHODS: CSE of different concentrations (0%, 0.25%, 0.5% and 1%) was co-cultured for 2 or 3 days with RLE-6TN, either pre-treated or not pre-treated with siRNA-PLTP for 6 h. Expression levels of E-cadherin mRNA and Vimentin mRNA were examined by RT-PCR, while expression levels of PLTP, E-cadherin, N-cadherin and Vimentin were examined by Western blot. RESULTS: Our results showed that the expression of E-cadherin mRNA decreased in CSE-treated groups: 1.01±0.05, 0.74±0.05, 0.65±0.03, 0.30±0.08 respectively at different concentrations of CSE (0 %, 0.25%, 0.5 %, and 1.0%); while the level of Vimentin mRNA increased significantly in 1% CSE treated cells(1.88±0.49), compared with control cells (1.01±0.20). Treatment with CSE at different concentrations (0%, 0.25%, 0.5% and 1%) showed that the protein levels of PLTP were 0.42±0.02, 0.89±0.25, 1.08±0.18, 1.61±0.06 respectively; those of E-cadherin were 1.61±0.04, 1.08±0.10, 0.62±0.08, 0.68±0.17, respectively; those of N-cadherin were 0.60±0.14, 0.57±0.26, 0.88±0.30, 1.94±0.54, respectively; and those of Vimentin were 0.61±0.05, 0.98±0.16, 1.07±0.14, 1.34±0.19, respectively; all P<0.05 when the 1% CSE group was compared with the control group. EMT induced by CSE was significantly inhibited by siRNA-PLTP. CONCLUSION: PLTP may be involved in CSE induced EMT of rat alveolar cells.

Synergistic activity of magnolol with azoles and its possible antifungal mechanism against Candida albicans.

AIM: The goal of this study was to investigate the synergic effects between magnolol and azoles, and the potential antifungal mechanisms. METHODS AND RESULTS: Microdilution checkerboard, time-kill and agar diffusion assay were employed to evaluate the synergic effects between magnolol and fluconazole (FLC). Magnolol significantly decreased the efflux of rhodamine 123 (Rh123), leading to greater intracellular accumulation of Rh123 in Candida albicans cells. Compared to the Candida drug resistance (cdr) 2 or multidrug resistance (mdr) 1 deletion mutant, the growth of cdr1 strain was most sensitive to magnolol exposure. In the presence of magnolol, MDR1 overexpressing cells were sensitive to FLC, whereas CDR1 and CDR2 overexpressing cells displayed tolerance to FLC. Magnolol treatment correlated with up-regulation of transporter and ergosterol biosynthesis pathway genes, analyzed by real-time reverse transcription-polymerase chain reaction. The ergosterol content of C. albicansSC5314 was significantly decreased after magnolol exposure. CONCLUSIONS: Magnolol synergizes with azoles for targeting of C. albicans by inducing a higher intracellular content of antifungals, by tapping into the competitive effect of ABC transporter Cdr1p substrates, and enhancing the effect by targeting of the ergosterol biosynthesis pathway. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results provide the first evidence that magnolol may function as a Cdr1p substrate and as an inhibitor of ergosterol biosynthesis. This function can thus be exploited in combination with azoles to reverse multidrug resistance of C. albicans strains.

Zopiclone use associated with increased risk of acute pancreatitis: a case-control study in Taiwan.

BACKGROUND: The purpose of this study was to assess the relationship between zopiclone use and the risk of acute pancreatitis in Taiwan. METHODS: This was a population-based case-control study. The data source was from the database of the Taiwan National Health Insurance Program since 2000-2011. We identified 5169 subjects aged 20-84 years with a first-time attack of acute pancreatitis as the patients and 20,676 sex-matched and age-matched subjects without acute pancreatitis as the controls. Active use of zopiclone was defined as subjects who received at least one prescription for zopiclone within 30 days before the date of diagnosing acute pancreatitis. The lack of zopiclone prescription was defined as 'never use'. We calculated the odds ratio (OR) and 95% confidence interval (CI) to assess the risk of acute pancreatitis associated with zopiclone use by the multivariable logistic regression model. RESULTS: After adjustment for potential confounding variables, the adjusted OR of acute pancreatitis was 2.36 for subjects with active use of zopiclone (95% CI 1.70-3.28), as compared with those with never use of zopiclone. In further analysis, as a reference of subjects with never use of zopiclone and without alcohol-related disease and biliary stone, the adjusted OR increased to 14.44 in those with active use of zopiclone and with alcohol-related disease or biliary stone (95% CI 7.47-27.89). CONCLUSIONS: Subjects actively using zopiclone are associated with increased risk of acute pancreatitis. Clinicians should take acute pancreatitis risk into account when prescribing zopiclone, particularly comorbid with alcohol-related disease or biliary stone.

Increased risk of acute pancreatitis following pneumococcal pneumonia: a nationwide cohort study.

BACKGROUND: The purpose of this study was to evaluate the risk of acute pancreatitis following pneumococcal pneumonia in Taiwan. METHODS: We undertook a retrospective cohort study using the hospitalisation claims data of the Taiwan National Health Insurance Program. We identified 16709 subjects aged 20-84 with the first-attack of pneumococcal pneumonia between 1998 and 2010 as the pneumonia group and we randomly selected 66836 subjects without a history of pneumonia as the non-pneumonia group. Both groups were matched for gender, age and index year. We examined the incidence of acute pancreatitis by the end of 2010 and we used a multivariable Cox proportional hazards regression model to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) of acute pancreatitis associated with pneumococcal pneumonia and other comorbidities. RESULTS: Subjects with pneumococcal pneumonia had higher incidence of acute pancreatitis, when compared with non-pneumonia subjects (2.41 vs. 1.47 per 1000 person-years, crude HR 1.65, 95% CI=1.38, 1.97). The highest risk of developing acute pancreatitis occurred during the first 3 months after diagnosing pneumococcal pneumonia (crude HR 4.11, 95% CI 1.98, 8.52). After adjusted for potential confounders, the adjusted HR of acute pancreatitis was 1.51 (95% CI 1.25, 1.82) for the pneumonia group, as compared with the non-pneumonia group. CONCLUSIONS: Overall, this study reveals a 51% increased hazard of acute pancreatitis following infection with pneumococcal pneumonia. Patients with pneumococcal pneumonia should receive close surveillance for risk of developing acute pancreatitis during the first 3 months after diagnosing pneumococcal pneumonia.

Hearing loss may be a non-motor feature of Parkinson's disease in older people in Taiwan.

BACKGROUND AND PURPOSE: The aim of this study was to explore whether hearing loss is associated with the risk of Parkinson's disease in the elderly in Taiwan. METHODS: Using claims data of the Taiwan National Health Insurance Program, 4976 patients (aged 65 years or older) with newly diagnosed hearing loss from 2000 to 2010 were identified and 19 904 subjects without hearing loss were randomly selected as comparisons, frequency matched by sex, age and index year of diagnosing hearing loss. The incidence of Parkinson's disease by the end of 2010 and the associated risk factors were investigated. RESULTS: The incidence of Parkinson's disease in the hearing loss group was 1.77-fold higher than that in the non-hearing-loss group (3.11 vs. 1.76 per 1000 person-years). After controlling for confounding factors, the adjusted hazard ratio (HR) of Parkinson's disease was 1.53 (95% CI 1.17, 1.99) for the hearing loss group compared with the non-hearing-loss group. Male sex (HR = 1.33, 95% CI 1.02, 1.74), age (for each year, HR = 1.06, 95% CI 1.04, 1.09), hypertension (HR = 1.70, 95% CI 1.26, 2.30) and cerebrovascular disease (HR = 1.78, 95% CI 1.37, 2.32) were also significantly associated with the risk of Parkinson's disease. CONCLUSIONS: Hearing loss correlates with an increased risk of Parkinson's disease in the elderly. Further studies are needed to confirm whether hearing loss could be a non-motor feature of Parkinson's disease.

Increased risk of pulmonary tuberculosis among patients with appendectomy in Taiwan.

The aim of this study was to determine whether there is a relationship between appendectomy and pulmonary tuberculosis in Taiwan. We designed a case-control study by analyzing the database from the Taiwan National Health Insurance Program. In total, we found 11,366 individuals (aged 20 years and older) with newly diagnosed pulmonary tuberculosis as the case group and 45,464 individuals without pulmonary tuberculosis as the control group from 1998 to 2011. The case group and the control group were matched on sex, age, and index year of diagnosing pulmonary tuberculosis. Using the multivariable unconditional logistic regression model, we measured the odds ratio (OR) and 95 % confidence interval (CI) for the risk of pulmonary tuberculosis associated with appendectomy and other comorbidities. After controlling for covariables, the multivariable unconditional logistic regression model disclosed that the OR of pulmonary tuberculosis was 1.4 in appendectomized patients (95 % CI = 1.13, 1.75) when compared to individuals without appendectomy. In further analysis, comorbidity with chronic obstructive pulmonary diseases (OR = 4.63, 95 % CI = 3.21, 6.68), pneumoconiosis (OR = 7.80, 95 % CI = 1.43, 42.5), chronic kidney diseases (OR = 5.65, 95 % CI = 1.79, 17.8), or diabetes mellitus (OR = 2.11, 95 % CI = 1.30, 3.44) increased the risk of pulmonary tuberculosis in appendectomized patients. Individuals with appendectomy are at a 1.4-fold increased risk of pulmonary tuberculosis. Comorbidities, including chronic obstructive pulmonary disease, pneumoconiosis, chronic kidney diseases, and diabetes mellitus, enhance the risk of pulmonary tuberculosis.

Reversal of MYB-dependent suppression of MAFB expression overrides leukaemia phenotype in MLL-rearranged AML.

The transcription factor MYB plays a pivotal role in haematopoietic homoeostasis and its aberrant expression is involved in the genesis and maintenance of acute myeloid leukaemia (AML). We have previously demonstrated that not all AML subtypes display the same dependency on MYB expression and that such variability is dictated by the nature of the driver mutation. However, whether this difference in MYB dependency is a general trend in AML remains to be further elucidated. Here, we investigate the role of MYB in human leukaemia by performing siRNA-mediated knock-down in cell line models of AML with different driver lesions. We show that the characteristic reduction in proliferation and the concomitant induction of myeloid differentiation that is observed in MLL-rearranged and t(8;21) leukaemias upon MYB suppression is not seen in AML cells with a complex karyotype. Transcriptome analyses revealed that MYB ablation produces consensual increase of MAFB expression in MYB-dependent cells and, interestingly, the ectopic expression of MAFB could phenocopy the effect of MYB suppression. Accordingly, in silico stratification analyses of molecular data from AML patients revealed a reciprocal relationship between MYB and MAFB expression, highlighting a novel biological interconnection between these two factors in AML and supporting new rationales of MAFB targeting in MLL-rearranged leukaemias.

Bacteriophages are synergistic with bacterial interference for the prevention of Pseudomonas aeruginosa biofilm formation on urinary catheters.

AIMS: We hypothesized that pretreating urinary catheters with benign Escherichia coli HU2117 plus an antipseudomonal bacteriophage (ΦE2005-A) would prevent Pseudomonas aeruginosa biofilm formation on catheters--a pivotal event in the pathogenesis of catheter-associated urinary tract infection (CAUTI). METHODS AND RESULTS: Silicone catheter segments were exposed to one of four pretreatments (sterile media; E. coli alone; phage alone; E. coli plus phage), inoculated with P. aeruginosa and then incubated up to 72 h in human urine before rinsing and sonicating to recover adherent bacteria. Pseudomonas aeruginosa adherence to catheters was almost 4 log(10) units lower when pretreated with E. coli plus phage compared to no pretreatment (P < 0.001) in 24-h experiments and more than 3 log(10) units lower in 72-h experiments (P < 0.05). Neither E. coli nor phage alone generated significant decreases. CONCLUSIONS: The combination of phages with a pre-established biofilm of E. coli HU2117 was synergistic in preventing catheter colonization by P. aeruginosa. SIGNIFICANCE AND IMPACT OF THE STUDY: We describe a synergistic protection against colonization of urinary catheters by a common uropathogen. Escherichia coli-coated catheters are in clinical trials; adding phage may offer additional benefit.

Scaling the dynamic electron scattering in imaging the graphene sheets by the high-angle annular dark-field microscopy.

Employing the graphene sheets (GSs), the electron scattering constants are measured in the high-angle annular dark-field (HAADF) imaging by the scanning transmission electron microscopy. Single scattering is found to be dominant until the layer number of 200, complying with a simple relation of I = Io(1 - e(-tau/lambda)). The discrete layer counting of the GSs enables precise determination of incident depths. This work results values of lambda = 48.2, 61.4, 97.9 and 115.6 nm for 80, 120, 160 and 200 keV electrons, respectively. The uncertainties with the mean free paths and the cross sections are confined to 10 percent. The dependences on the electron beam energy and the collection angle are discussed based on a multislice simulation.