Antimicrobial resistance (AMR) is a major public health problem that requires publicly available tools for rapid analysis. To identify AMR genes in whole-genome sequences, the National Center for ...Biotechnology Information (NCBI) has produced AMRFinder, a tool that identifies AMR genes using a high-quality curated AMR gene reference database. The Bacterial Antimicrobial Resistance Reference Gene Database consists of up-to-date gene nomenclature, a set of hidden Markov models (HMMs), and a curated protein family hierarchy. Currently, it contains 4,579 antimicrobial resistance proteins and more than 560 HMMs. Here, we describe AMRFinder and its associated database. To assess the predictive ability of AMRFinder, we measured the consistency between predicted AMR genotypes from AMRFinder and resistance phenotypes of 6,242 isolates from the National Antimicrobial Resistance Monitoring System (NARMS). This included 5,425
, 770
spp., and 47
isolates phenotypically tested against various antimicrobial agents. Of 87,679 susceptibility tests performed, 98.4% were consistent with predictions. To assess the accuracy of AMRFinder, we compared its gene symbol output with that of a 2017 version of ResFinder, another publicly available resistance gene detection system. Most gene calls were identical, but there were 1,229 gene symbol differences (8.8%) between them, with differences due to both algorithmic differences and database composition. AMRFinder missed 16 loci that ResFinder found, while ResFinder missed 216 loci that AMRFinder identified. Based on these results, AMRFinder appears to be a highly accurate AMR gene detection system.
Self-assembly of rigid building blocks with explicit shape and symmetry is substantially influenced by the geometric factors and remains largely unexplored. We report the selective assembly behaviors ...of a class of precisely defined, nanosized giant tetrahedra constructed by placing different polyhedral oligomeric silsesquioxane (POSS) molecular nanoparticles at the vertices of a rigid tetrahedral framework. Designed symmetry breaking of these giant tetrahedra introduces precise positional interactions and results in diverse selectively assembled, highly ordered supramolecular lattices including a Frank-Kasper A15 phase, which resembles the essential structural features of certain metal alloys but at a larger length scale. These results demonstrate the power of persistent molecular geometry with balanced enthalpy and entropy in creating thermodynamically stable supramolecular lattices with properties distinct from those of other self-assembling soft materials.
Mass rapid transit (MRT) systems are the backbone of transportation infrastructure in many cities. During emergencies, indoor subway stations become particularly susceptible to panic and ...overcrowding, making evacuation difficult. Therefore, simulating the evacuation and sheltering processes of a large number of individuals during emergencies is key in urban disaster response. In this study, a spatial evacuation risk model was used to enhance the safety of evacuation strategies in an MRT system. Data were collected on spatial architectural floor plans, and a database for communication and pedestrian flow was established. The behavioral patterns and distribution of individuals within stations and the characteristics of refuge spaces were also investigated. To simulate the processes of evacuation and sheltering, the Pathfinder evacuation simulation tool was used to construct a three-dimensional spatial model of a subway station. Specific scenarios were then constructed to simulate the procedures of evacuation and sheltering. Subsequently, the factors contributing to overcrowding-related hazards were analyzed to examine the spatial risks associated with crowd aggregation and evacuation and provide recommendations for improvement. Given its numerous advantages, this approach can serve as a valuable reference for conducting risk assessments in other large-scale crowd aggregation spaces.
Frank-Kasper phases, a family of ordered structures formed from particles with spherical motifs, are found in a host of materials, such as metal alloys, inorganic colloids and various types of soft ...matter. All the experimentally observed Frank-Kasper phases can be constructed from the basic units of three fundamental structures called the A15, C15 and Z phases. The Z phase, typically observed in metal alloys, is associated with a relatively large volume ratio between its constituents, and this constraint inhibits its formation in most self-assembled single-component soft-matter systems. We have assembled a series of nanosized shape amphiphiles that comprise a triphenylene core and six polyhedral oligomeric silsesquioxane cages grafted onto it through linkers to give a variety of unconventional structures, which include the Z phase. This structure was obtained through fine tuning of the linker lengths between the core and the peripheral polyhedral oligomeric silsesquioxane cages, and exhibits a relatively large volume asymmetry between its constituent polyhedral particle motifs.
A key focus in the field of drug discovery has been motivated by the neuroprotection of natural compounds. Cerebral ischemia is a multifaceted pathological process with a series of mechanisms, and a ...perspective for the development of neuroprotectants from traditional herbal medicine or natural products is a promising treatment for this disease. Natural compounds with the effects of anti-oxidation, anti-inflammation, anti-apoptosis, and neurofunctional regulation exhibit therapeutic effects on experimental ischemic brain injury. Conferring to the pharmacological mechanisms underlying neuroprotection, a study found that androgapholide, a diterpene lactone compound, exhibits varying degrees of neuroprotective activities in both in vitro and in vivo experimental models of stroke. The neuroprotective mechanisms of andrographolide are suggested as: (I) increasing nuclear factor E2-related factor 2-heme oxygenase (Nrf2-HO-1) expression through p38-mitogen activated protein kinase (MAPK) regulation, (II) inducing cerebral endothelial cells (CEC) apoptosis and caspase-3 activation, (III) down regulating Bax, inducible nitric oxide synthase (iNOS), and (IV) inhibiting hydroxyl radical (OH
) formation, and activating transcription factor NF-κB signaling pathways. Recently, several researchers have also been trying to unveil the principal mechanisms involved in the neuroprotective effects of andrographolide. Therefore, this review aims to summarize an overview on the neuroprotective effects of andrographolide and exemplifies the essential mechanisms involved. This paper can provide information that andrographolide drug discovery may be a promising strategy for the development of a novel class of neuroprotective drug.
Background
Fibrosis‐4 score (FIB4) was a non‐invasive surrogate to estimate the amount of liver scarring in chronic hepatitis. Considering the presence of increased central venous pressure and ...congestive hepatopathy in patients with decompensated heart failure, we therefore investigated the prognostic values of FIB4 in acute heart failure (AHF) patients.
Method
Patients hospitalised primarily for HF were drawn from an intramural registry. FIB4 was calculated according to age, aspartate aminotransferase, alanine aminotransferase and platelet count. All‐cause mortality up to 5 years after discharge was obtained by linking to the national death registry.
Results
Among a total of 1854 participants, 940 patients died during a mean follow‐up of 28.3 ± 21.8 months. FIB4 score was related to mortality and the composite of cardiovascular death or HF rehospitalisation, independent of age, sex, left ventricular ejection fraction, left atrial dimension, sodium and haemoglobin levels, estimated glomerular filtration rate, comorbidities, and medications hazard ratio and 95% confidence interval of mortality: 1.009 (1.002–1.015), and the composite of cardiovascular death or HF hospitalisation: 1.020 (1.010–1.031). The prognostic value of FIB4 was predominantly in the subjects with heart failure and preserved or mildly reduced ejection fraction (HFpEF and HFmrEF), or coronary artery disease (CAD) than the counterparts interaction p‐value <0.001, and 0.004, respectively.
Conclusions
FIB4 was an independent predictor of survival in AHF patients, irrespective of the phenotypes of HF. The higher predictive value of mortality of FIB4 was observed in the subjects with HFpEF, HFmrEF or CAD.
Development of acquired resistance to lapatinib, a dual epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitor, severely limits the duration ...of clinical response in advanced HER2‐driven breast cancer patients. Although the compensatory activation of the PI3K/Akt survival signal has been proposed to cause acquired lapatinib resistance, comprehensive molecular mechanisms remain required to develop more efficient strategies to circumvent this therapeutic difficulty. In this study, we found that suppression of HER2 by lapatinib still led to Akt inactivation and elevation of FOX3a protein levels, but failed to induce the expression of their downstream pro‐apoptotic effector p27kip1, a cyclin‐dependent kinase inhibitor. Elevation of miR‐221 was found to contribute to the development of acquired lapatinib resistance by targeting p27kip1 expression. Furthermore, upregulation of miR‐221 was mediated by the lapatinib‐induced Src family tyrosine kinase and subsequent NF‐κB activation. The reversal of miR‐221 upregulation and p27kip1 downregulation by a Src inhibitor, dasatinib, can overcome lapatinib resistance. Our study not only identified miRNA‐221 as a pivotal factor conferring the acquired resistance of HER2‐positive breast cancer cells to lapatinib through negatively regulating p27kip1 expression, but also suggested Src inhibition as a potential strategy to overcome lapatinib resistance.
The downregulation of p27kip1 by Src/NF‐κB axis‐induced miR‐221 expression as a novel mechanistic insight into lapatinib resistance. Targeting Src would be a promising strategy to overcome lapatinib resistance.
Dyed‐in‐the‐wool true blue: True‐blue phosphorescent organic light‐emitting diodes are fabricated by using an IrIII dopant (see picture; gray C; blue N; red Ir; green F). The Ir complex has an ...enhanced metal‐to‐ligand charge‐transfer contribution, hence a shortened radiative lifetime in the excited state. The maximum external quantum efficiency of the fabricated device is 8.5 % and the main emission is around 450 nm.
Organisms often acquire physiological and morphological modifications to conquer ecological challenges when colonizing new environments which lead to their adaptive evolution. However, deciphering ...the genomic mechanism of ecological adaptation is difficult because ecological environments are often too complex for straightforward interpretation. Thus, we examined the adaptation of a widespread songbird—the rufous‐capped babbler (Cyanoderma ruficeps)—to a relatively simple system: distinct environments across elevational gradients on the mountainous island of Taiwan. We focused on the genomic sequences of 43 birds from five populations to show that the Taiwan group split from its sister group in mainland China around 1–2 million years ago (Ma) and colonized the montane habitats of Taiwan at least twice around 0.03–0.22 Ma. The montane and lowland Taiwan populations diverged with gene flow between them, suggesting strong selection associated with different elevations. We found that the montane babblers had smaller beaks than the lowland ones, consistent with Allen's rule, and identified candidate genes—COL9A1 and SOX11—underlying the beak size changes. We also found that altitudinally divergent mutations were mostly located in noncoding regions and tended to accumulate in chromosomal inversions and autosomes. The altitudinally divergent mutations might regulate genes related to haematopoietic, metabolic, immune, auditory and vision functions, as well as cerebrum morphology and plumage development. The results reveal the genomic bases of morphological and physiological adaptation in this species to the low temperature, hypoxia and high UV light environment at high elevation. These findings improve our understanding of how ecological adaptation drives population divergence from the perspective of genomic architecture.
The availability of intense, ultrashort coherent radiation sources in the infrared region of the spectrum is enabling the generation of attosecond X-ray pulses via high-harmonic generation, ...pump–probe experiments in the ‘molecular fingerprint’ region and opening up the area of relativistic infrared nonlinear optics of plasmas. These applications would benefit from multi-millijoule single-cycle pulses in the mid- to long-wavelength infrared region. Here, we present a new scheme capable of producing tunable relativistically intense, single-cycle infrared pulses from 5 to 14 μm with a 1.7% conversion efficiency based on a photon frequency downshifting scheme that uses a tailored plasma density structure. The carrier-envelope phase of the long-wavelength infrared pulse is locked to that of the drive laser to within a few per cent. Such a versatile tunable infrared source may meet the demands of many cutting-edge applications in strong-field physics and greatly promote their development.
PDF
