Stochastic DNA walkers capable of traversing on three-dimensional (3D) tracks have received great deal of attention. However, DNA walker-based biosensors exhibit limited amplification efficiency ...because of their slow walking kinetics and low processivity. Herein, by taking advantage of the high processivity of a DNA rolling machine, a sensitive ratiometric DNA nanomachine biosensor is designed. The biosensor is constructed with hairpin-loaded Au nanoparticles (NPs) (hpDNA@AuNPs) as a DNA walker and AgNCs-decorated magnetic NPs (AgNCs@MNPs) as a DNA rolling machine. In the presence of target DNA, exonuclease III (Exo III)-powered DNA walker is activated to accomplish first-stage amplification via a burnt-bridge mechanism, generating a great deal of toehold-loaded AuNPs (Toehold@AuNPs) to hybridize with magnetic nanoparticles loaded with silver-nanoclusters-labeled DNA (AgNCs@MNPs) with the assistance of Exo III. These trigger rapid rolling of AuNPs on the AgNCs@MNPs surface and release free AgNCs, converting the biological signal into a mass spectrometric signal ratio (107Ag/197Au) with detection by ICP-MS. A linear range of 0.5–500 fmol L–1 is achieved with a detection limit of 119 amol L–1 for the p53 gene. The practical applicability of the biosensor has been demonstrated in the accurate assay of the p53 gene in the human blood.
The fictive temperature (Tf) is widely applied to understand the relaxation thermodynamics of a glass; however, its atomic structural origin is still unclear. Here, we report two novel AZnP3O9 ...glasses obtained by melting the composition identical single crystals. These glasses exhibit structural inheritance within 5 Å from the single crystal counterparts that is quantified by δ=nglass/ncry (0≤δ≤1, n is the number of pair correlation functions). Among the available glass‐formers, glassKZnP3O9 exhibits the highest structural inheritance (δ=1, nglass=8). More insightfully, a reverse correlation between δ and the relaxation thermodynamic parameters is observed in glassAZnP3O9, revealing for the first time the atomic structural origin of fictive temperature.
A new evaluation method is provided to judge the glass stability and glass‐forming ability. As an example, the reported novel glass KZnP3O9 exhibits the highest δ (δ=1, nglass=8) that quantitatively identifies the short‐range order similarity to its crystalline counterpart. The inverse δ‐Tf correlation gives the direct evidence for the structural origin of fictive temperature revealing the relaxation thermodynamics.
The unique features of uniform and adjustable cavities, abundant chiral active sites, and high enantioselectivity make chiral metal‐organic frameworks popular as an emerging candidate for ...enantioselective separation. However, the wide particle size distribution and irregular shape of as‐synthesized metal–organic frameworks result in low column efficiency, undesired chromatographic peak shape, and high column backpressure of such metal–organic frameworks packed columns. Herein, we report the fabrication of chiral core‐shell microspheres Cu2(d‐Cam)2(4,4′‐bpy)n@SiO2 composite for high‐performance liquid chromatography enantioseparation to overcome the above‐mentioned problems. The Cu2(d‐Cam)2(4,4′‐bpy)n@SiO2 packed column gave high‐resolution separation of racemates under low column backpressure (10‐22 bar), indicating its synergistic effect of the good column packing property of the SiO2 microspheres and the chiral recognition ability of Cu2(d‐Cam)2(4,4′‐bpy)n crystals. Thirteen kinds of chiral compounds including alcohols, amines, ketones, epoxides, and organic bases were well separated with good peak shapes and high column efficiency (18200 plates/m for 1‐(9‐anthryl)‐2,2,2‐trifluoroethanol) on the Cu2(d‐Cam)2(4,4′‐bpy)n@SiO2 packed column. Among them, seven pairs of enantiomers achieved baseline separation and the resolution value for 1‐(9‐anthryl)‐2,2,2‐trifluoroethanol reached 11.22. Some effects such as column temperature, and analytes mass on the enantioseparations have been investigated. In addition, the Cu2(d‐Cam)2(4,4′‐bpy)n@SiO2 packed column exhibited good stability and repeatability for the separation of chiral compounds. The relative standard deviations for five replicate separations of 1‐phenylethanol were less than 1.0, 1.5, 3.0, and 2.0% for the retention time, peak area, number of theoretical plates, and resolution, respectively. The research results demonstrated the development of chiral metal–organic frameworks core‐shell microspheres composite provide a promising platform for their practical application in chiral separation fields.
Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the ...SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.
To determine the annual incidences and rates of progression of myopia and high myopia in Chinese schoolchildren from grade 1 to grade 6 and explore the possible cause-specific risk factors for ...myopia.
From 11 randomly selected primary schools in Anyang city, central China, 2835 grade 1 students were examined with annual follow ups for 5 years. Students were invited to undergo a comprehensive examination, including cycloplegic autorefraction, ocular biometry, and standardized questionnaires.
The mean spherical equivalent refraction decreased substantially from +0.94 ± 1.03 diopter (D) in grade 1 to -1.37 ± 2.08 D in grade 6, with rapid annual myopic shifts, especially for students in grades 3 through 6 (-0.51 to -0.59 D). The prevalence of myopia increased substantially, with the yearly incidence of myopia increasing from 7.8% in grade 1 and 2 to 25.3% in grades 5 and 6, and the incidence of high myopia increased from 0.1% to 1.0%. The 5-year incidence of myopia was lowest among children who has a baseline spherical equivalent refraction of greater than +2.00 D (4.4%), and increased to nearly 92.0% among children whose baseline spherical equivalent refraction was 0.00 to -0.50 D. The incidence of myopia was higher in children who had less hyperopic baseline refraction, two myopic parents, longer axial length, deeper anterior chamber, higher axial length-corneal radius of curvature ratio, and thinner lenses.
Both the annual incidence and progression rates of myopia and high myopia were high in Chinese schoolchildren, especially after grade 3. Hyperopic refraction of children should be monitored before primary school as hyperopia reserve to prevent the onset of myopia and high myopia.
Studies on relations between arterial stiffness and full spectrum of radiological features of cerebral small vessel disease (CSVD) are scarce. We aim to investigate the association of arterial ...stiffness with lacunes, white matter hyperintensities (WMH), microbleeds (CMBs), dilated perivascular spaces (PVS), and brain atrophy in a community-based sample.
A total of 953 participants (55.7 ± 9.4 years) who underwent brachial-ankle pulse wave velocity (baPWV) and brain magnetic resonance imaging were included. Lacunes, CMBs, and PVS were visually rated. Brain structure and WMH were automatically segmented. Brain parenchyma fraction (BPF), a surrogate index of brain atrophy, was calculated as a ratio of brain parenchyma volume to total intracranial volume. Multivariable logistic and linear regressions were used to investigate the associations between baPWV and CSVD. Subsequently, we explored these associations in strata of age.
Increased baPWV was associated with severe PVS in white matter (OR, 1.09; 95%CI, 1.01-1.17;
= 0.022), larger WMH volume (β, 0.08; 95%CI, 0.04-0.12;
< 0.001), lower BPF (β, -0.09; 95%CI, -0.15- -0.03;
= 0.007), and marginally associated with strictly lobar CMBs (OR, 1.11; 95%CI, 1.00-1.23;
= 0.055), but not with lacunes. WMH volume mediated the relation between baPWV and BPF. In age subgroup analysis, the association of baPWV with PVS in white matter was stronger among those aged <55 years, whereas the association with brain atrophy was more prominent among those aged ≥55 years. Increased baPWV was associated with larger WMH volume in both younger and older individuals.
Increased arterial stiffness was associated with most of imaging markers of CSVD, including PVS in white matter, larger WMH volume, strictly lobar CMBs, and brain atrophy, but not lacunes. The mechanisms underlying these associations and their potential clinical significances warrant further investigations.
This paper addresses deep face recognition (FR) problem under open-set protocol, where ideal face features are expected to have smaller maximal intra-class distance than minimal inter-class distance ...under a suitably chosen metric space. However, few existing algorithms can effectively achieve this criterion. To this end, we propose the angular softmax (A-Softmax) loss that enables convolutional neural networks (CNNs) to learn angularly discriminative features. Geometrically, A-Softmax loss can be viewed as imposing discriminative constraints on a hypersphere manifold, which intrinsically matches the prior that faces also lie on a manifold. Moreover, the size of angular margin can be quantitatively adjusted by a parameter m. We further derive specific m to approximate the ideal feature criterion. Extensive analysis and experiments on Labeled Face in the Wild (LFW), Youtube Faces (YTF) and MegaFace Challenge 1 show the superiority of A-Softmax loss in FR tasks.
Medical visual question answering (Med-VQA) aims to accurately answer a clinical question presented with a medical image. Despite its enormous potential in healthcare services, the development of ...this technology is still in the initial stage. On the one hand, Med-VQA tasks are highly challenging due to the massive diversity of clinical questions that require different visual reasoning skills for different types of questions. On the other hand, medical images are complex in nature and very different from natural images, while current Med-VQA datasets are small-scale with a few hundred radiology images, making it difficult to train a well-performing visual feature extractor. This paper addresses above two critical issues. We propose a novel conditional reasoning mechanism with a question-conditioned reasoning component and a type-conditioned reasoning strategy to learn effective reasoning skills for different Med-VQA tasks adaptively. Further, we propose to pre-train a visual feature extractor for Med-VQA via contrastive learning on large amounts of unlabeled radiology images. The effectiveness of our proposals is validated by extensive experiments on existing Med-VQA benchmarks, which show significant improvement of our model in prediction accuracy over state-of-the-art methods. The source code and pre-training dataset are provided at https://github.com/Awenbocc/CPCR .
A symmetrical dual-beam end-fire bowtie antenna with gain enhancement is achieved by integrating three pairs of metamaterial (MTM) arrays for 5G MIMO applications. The first pair of MTM array with ...high refractive index (HRI) are deployed to form a wide beam antenna. The second pair of HRI MTM array are arranged along the end-fire direction ( x -direction) in front of the radiators in order to split the single wide beam into dual beam. Besides, the third pair of anisotropic MTM array with HRI along x -direction and near zero refractive along y -direction are incorporated in front of the second pair of MTM array to improve the gain performance. The proposed technique is verified by both the full-wave electromagnetic simulation and experiment, and the simulated and measured results agree very well with each other. Moreover, the measured results reveal that the main beam directions of the proposed antenna point to <inline-formula><tex-math notation="LaTeX">\pm 30^{\circ }</tex-math></inline-formula> with respect to the end-fire direction (0<inline-formula><tex-math notation="LaTeX">^{\circ }</tex-math></inline-formula>) over 24.25-27.5 GHz, with a maximum gain of 7.4 dBi at 26 GHz and a 4.2 dB gain improvement compared to the wide beam antenna.
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