Urinary tract infection (UTI) is one of the most common outpatient bacterial infections. In this study, we isolated and characterized an extensively-drug resistant (XDR) NDM-5-producing Escherichia ...coli EC1390 from a UTI patient by using whole-genome sequencing (WGS) in combination with phenotypic assays.
Antimicrobial susceptibility to 23 drugs was determined by disk diffusion method. The genome sequence of EC1390 was determined by Nanopore MinION MK1C platform. Conjugation assays were performed to test the transferability of EC1390 plasmids to E. coli recipient C600. Phenotypic assays, including growth curve, biofilm formation, iron acquisition ability, and cell adhesion, were performed to characterize the function of EC1390 plasmids.
Our results showed that EC1390 was only susceptible to tigecycline and colistin, and thus was classified as XDR E. coli. A de novo genome assembly was generated using Nanopore 73,050 reads with an N
value of 20,936 bp and an N
value of 7,624 bp. WGS analysis showed that EC1390 belonged to the O101-H10 serotype and phylogenetic group A E. coli. Moreover, EC1390 contained 2 conjugative plasmids with a replicon IncFIA (pEC1390-1 with 156,286 bp) and IncFII (pEC1390-2 with 71,840 bp), respectively. No significant difference was observed in the bacterial growth rate in LB broth and iron acquisition ability between C600, C600 containing pEC1390-1, C600 containing pEC1390-2, and C600 containing pEC1390-1 and pEC1390-2. However, the bacterial growth rate in nutrition-limited M9 broth was increased in C600 containing pEC1390-2, and the cell adhesion ability was increased in C600 containing both pEC1390-1 and pEC1390-2. Moreover, these plasmids modulated the biofilm formation under different conditions.
In summary, we characterized the genome of XDR-E. coli EC1390 and identified two plasmids contributing to the antimicrobial resistance, growth of bacteria in a nutrition-limited medium, biofilm formation, and cell adhesion.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Multidrug resistance (MDR) remains a significant challenge in cancer therapy, with inherent and acquired resistance distinct. While conventional drug selection processes enable the isolation of ...cancer cells with acquired multidrug resistance, identifying cancer cells with inherent drug resistance remains challenging. Herein, we proposed a molecular beacon (MB)-based strategy to identify and isolate the inherent MDR cancer cells. A lipid/PLGA core-shell nanoparticulate system (DNCP) was designed to deliver MB for intracellular MDR1 mRNA imaging. DNCP-MB – possess a surface potential of −8 mV and a size of 150 nm – demonstrated effective delivery of MB, remarkable selectivity towards the selected intracellular mRNA targets, and low cytotoxicity. Following DNCP transfection, fluorescence-activated cell sorting (FACS) was employed to differentiate MCF-7 cells into two distinct sub-populations: the Top 10 cells with a high level of MDR gene expression and the Bottom 10 cells with a low level of MDR gene expression, which represent inherent drug-resistant and non-drug-resistant cells, respectively. Intriguingly, we observed a positive correlation between elevated MDR1 mRNA expression and increased migration, enhanced proliferation rate, and tighter spheroid formation. Moreover, we conducted RNA sequencing analysis on the Top 10, Bottom 10, and MCF-7/ADR cells. The findings revealed a notable disparity in the gene ontology enrichment analysis of differentially expressed genes between the Top 10 and Bottom 10 cells when compared to the Bottom 10 and MCF-7/ADR cells. This novel approach provides a promising avenue for isolating inherent drug-resistant cells and holds significant potential in unraveling the mechanisms underlying inherent drug resistance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Background
Ubiquitous presence of short extrachromosomal circular DNAs (eccDNAs) in eukaryotic cells has perplexed generations of biologists. Their widespread origins in the genome lacking ...apparent specificity led some studies to conclude their formation as random or near-random. Despite this, the search for specific formation of short eccDNA continues with a recent surge of interest in biomarker development.
Results
To shed new light on the conflicting views on short eccDNAs’ randomness, here we present DeepCircle, a bioinformatics framework incorporating convolution- and attention-based neural networks to assess their predictability. Short human eccDNAs from different datasets indeed have low similarity in genomic locations, but DeepCircle successfully learned shared DNA sequence features to make accurate cross-datasets predictions (accuracy: convolution-based models: 79.65 ± 4.7%, attention-based models: 83.31 ± 4.18%).
Conclusions
The excellent performance of our models shows that the intrinsic predictability of eccDNAs is encoded in the sequences across tissue origins. Our work demonstrates how the perceived lack of specificity in genomics data can be re-assessed by deep learning models to uncover unexpected similarity.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gut microbiota have been targeted by alternative therapies for non-communicable diseases. We examined the gut microbiota of a healthy Taiwanese population, identified various bacterial drivers in ...different demographics, and compared them with dialysis patients to associate kidney disease progression with changes in gut microbiota.
This was a cross-sectional cohort study.
Fecal samples were obtained from 119 healthy Taiwanese volunteers, and 16S rRNA sequencing was done on the V3-V4 regions to identify the bacterial enterotypes. Twenty-six samples from the above cohort were compared with fecal samples from 22 peritoneal dialysis and 16 hemodialysis patients to identify species-level bacterial biomarkers in the dysbiotic gut of chronic kidney disease (CKD) patients.
Specific bacterial species were identified pertaining to different demographics such as gender, age, BMI, physical activity, and sleeping habits. Dialysis patients had a significant difference in gut microbiome composition compared to healthy controls. The most abundant genus identified in CKD patients was
, and at the species level hemodialysis patients showed significant abundance in
,
, and peritoneal dialysis patients showed higher abundance in
(p ≤ 0.05) than the control group. Pathways pertaining to the production of uremic toxins were enriched in CKD patients. The abundance of the bacterial species depended on the type of dialysis treatment.
This study characterizes the healthy gut microbiome of a Taiwanese population in terms of various demographics. In a case-control examination, the results showed the alteration in gut microbiota in CKD patients corresponding to different dialysis treatments. Also, this study identified the bacterial species abundant in CKD patients and their possible role in complicating the patients' condition.
Cu2O rhombic dodecahedra, octahedra, and cubes were densely modified with conjugated 4-ethynylaniline (4-EA) for facet-dependent photocatalytic activity examination. Infrared spectroscopy affirms ...bonding of the acetylenic group of 4-EA onto the surface copper atoms. The photocatalytically inactive Cu2O cubes showed surprisingly high activity toward methyl orange photodegradation after 4-EA modification, while the already active Cu2O rhombic dodecahedra and octahedra exhibited a photocatalytic activity enhancement. Electron, hole, and radical scavenger experiments prove that the photocatalytic charge transport processes have occurred in the functionalized Cu2O cubes. Electrochemical impedance spectroscopy also indicates reduced charge transfer resistance of the functionalized Cu2O crystals. A band diagram constructed from UV–vis spectral and Mott–Schottky measurements reveals significant band energy shifts in all Cu2O samples after decorating with 4-EA. From density functional theory (DFT) calculations, a new band has emerged slightly above the valence band maximum within the band gap of Cu2O, which has been found to originate from 4-EA through band-decomposed charge density analysis. The increased charge density localized on the 4-EA molecule and the smallest electron transition energy to reach the 4-EA-generated band are factors making {100}-bound Cu2O cubes photocatalytically active. Proper molecular decoration represents a powerful approach to improving the photocatalytic efficiency of semiconductors.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
This study aimed to characterize carbapenem-nonsusceptible Acinetobacter (CNSA) isolated from patients with bacteremia from 1997 to 2015.
A total of 173 CNSA (12.3%) was recovered from 1403 ...Acinetobacter isolates. The presence of selected β-lactamase genes in CNSA was determined by PCR amplification. The conjugation test was used to determine the transferability of metallo-β-lactamase (MBL)-carrying plasmids. Whole genome sequencing in combination with phenotypic assays was carried out to characterize MBL-plasmids.
In general, a trend of increasing numbers of CNSA was observed. Among the 173 CNSA, A. baumannii (54.9%) was the most common species, followed by A. nosocomialis (23.1%) and A. soli (12.1%). A total of 49 (28.3%) CNSA were extensively drug-resistant, and all were A. baumannii. The most common class D carbapenemase gene in 173 CNSA was blaOXA-24-like (32.4%), followed by ISAba1-blaOXA-51-like (20.8%), ISAba1-blaOXA-23 (20.2%), and IS1006/IS1008-blaOXA-58 (11.6%). MBL genes, blaVIM-11,blaIMP-1, and blaIMP-19 were detected in 9 (5.2%), 20 (11.6%), and 1 (0.6%) CNSA isolates, respectively. Transfer of MBL genes to AB218 and AN254 recipient cells was successful for 7 and 6 of the 30 MBL-plasmids, respectively. The seven AB218-derived transconjugants carrying MBL-plasmids produced less biofilm but showed higher virulence to larvae than recipient AB218.
Our 19-year longitudinal study revealed a stable increase in CNSA during 2005–2015. blaOXA-24-like, ISAba1-blaOXA-51-like, and ISAba1-blaOXA-23 were the major determinants of Acinetobacter carbapenem resistance. MBL-carrying plasmids contribute not only to the carbapenem resistance but also to A. baumannii virulence.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
COVID-19, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first broke out at the end of 2019. Despite rapidly spreading around the world during the first half of ...2020, it remained well controlled in Taiwan without the implementation of a nationwide lockdown. This study aimed to evaluate the PM2.5 concentrations in this country during the 2020 COVID-19 pandemic and compare them with those during the corresponding period from 2019. We obtained measurements (taken every minute or every 3 minutes) from approximately 1,500 PM2.5 sensors deployed in industrial areas of northern and southern Taiwan for the first quarters (January–March) of both years. Our big data analysis revealed that the median hourly PM2.5 levels decreased by 3.70% (from 16.3 to 15.7 µg m–3) and 10.6% (from 32.4 to 29.3 µg m–3) in the north and south, respectively, between these periods owing to lower domestic emissions of PM2.5 precursors (viz., nitrogen dioxide and sulfur dioxide) and, to a lesser degree, smaller transported emissions of PM2.5, e.g., from China. Additionally, the spatial patterns of the PM2.5 in both northern and southern Taiwan during 2020 resembled those from the previous year. Finally, controlling local PM2.5 emission sources critically contributes to reducing the number of COVID-19 cases.
MoSi2N4 has outstanding potential for applications in electronics, spintronics, and semiconducting fabrication. This attractive scenario can be attributed to its remarkable electronic properties. In ...this study, we investigate the electronic structure and optical spectra of the MSi2N4 (M = Mo, Ta, and V) materials with single atom (H, N, and O) decoration using first-principles calculations. Pristine MoSi2N4 and VSi2N4 are semiconductors, and TaSi2N4 shows the half-metal properties. Decorating MoSi2N4 with single hydrogen and nitrogen atoms induces a magnetic moment. Single oxygen decorated TaSi2N4 does not change its intrinsic electronic properties, which is suitable for spintronic applications. On top of that, the semiconductor VSi2N4 can be turned into a half-metal via single hydrogen atom decoration. The absorption spectra demonstrate an enhancement in optical absorption for VSi2N4 after the decoration with a single nitrogen atom. Single atom decoration is one of the effective methods of tailoring the electronic properties of the two-dimensional MoSi2N4 family. Our findings can accelerate the development of the advanced electronic devices.
Abstract
Integrating omics data with quantification of biological traits provides unparalleled opportunities for discovery of genetic regulators by in silico inference. However, current approaches to ...analyze genetic-perturbation screens are limited by their reliance on annotation libraries for prioritization of hits and subsequent targeted experimentation. Here, we present iTARGEX (identification of Trait-Associated Regulatory Genes via mixture regression using EXpectation maximization), an association framework with no requirement of a priori knowledge of gene function. After creating this tool, we used it to test associations between gene expression profiles and two biological traits in single-gene deletion budding yeast mutants, including transcription homeostasis during S phase and global protein turnover. For each trait, we discovered novel regulators without prior functional annotations. The functional effects of the novel candidates were then validated experimentally, providing solid evidence for their roles in the respective traits. Hence, we conclude that iTARGEX can reliably identify novel factors involved in given biological traits. As such, it is capable of converting genome-wide observations into causal gene function predictions. Further application of iTARGEX in other contexts is expected to facilitate the discovery of new regulators and provide observations for novel mechanistic hypotheses regarding different biological traits and phenotypes.
Graphical Abstract
Graphical Abstract
iTARGEX is an analytical tool that accounts for heterogeneity in transcriptional responses to single-gene deletion mutants to facilitate the discovery of new regulators and novel mechanistic hypotheses regarding different biological traits and phenotypes.
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