The receptor-binding domain (RBD) of spike recognizing the receptor angiotensin-converting enzyme 2 (ACE2) initiates membrane fusion between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and cell membrane. Although the structure of the RBD_ACE2 complex has been well studied, its functional mechanism in membrane fusion is still not fully understood. Here, using an in vitro cell-vesicle content-mixing assay, it is found that the cleavage at the S2' site by thrombin (Thr) protease strongly accelerates membrane fusion, compared to that of cleavage at the S1/S2 site by PreScission (3C) protease. Moreover, mutations at the RBD_ACE2 interface resulted in a positive correlation between binding affinity and fusion probability. In both the cell-vesicle and cell-cell fusion assays, by crosslinking two membranes via the neutravidin (NTV)_biotin interaction or complementary DNA strands, it is found that spike drives membrane fusion in the absence of ACE2, and a suitable distance between two membranes is critical for spike-mediated membrane fusion. Finally, unsuitable membrane crosslinkers significantly inhibited the fusion probability in the presence of ACE2. Taken together, the results suggest that the RBD_ACE2 complex may act as a crosslinker to bridge the viral and cell membranes at a suitable distance, which is critical, but also substitutable for spike-mediated SARS-CoV-2 entry.
Aim: To analyse the relationship between two potentially functional single-nucleotide polymorphisms (SNPs) of the miR-146a gene (rs2910164 and rs57095329) and the risk of atherosclerotic cerebral infarction (ACI). Methods: A total of 297 patients with ACI and 300 matched healthy individuals were enrolled in the study. The miR-146a polymorphism was detected using the polymerase chain reaction–restriction fragment length polymorphism method. Results: A significant difference in the C allele frequency at rs2910164 (p=0.028) was noted between patients with ACI and control subjects. In contrast, the genotype and allele frequencies of rs57095329 were not statistically associated with ACI. In addition, the decreased expression of miR-146a was significantly more frequent in ACI patients who were ApoEε4 (+) carriers (p=0.0233), and rs2910164 G>C was intimately associated with the ApoEε4-containing genotype in patients compared with the ApoEε4 (-) carriers (p=0.0323). Conclusions: Our findings indicated that the C allele of rs2910164 miR-146a is an important risk factor for ACI, and ApoEε4 may function through attenuating miR-146a expression to enhance ACI susceptibility. This study provides new information about the possible relationship between miR-146a and ApoEε4 in the development of ACI, with potentially important therapeutic implications.
This study demonstrates a feasible and efficient route to alleviate the absorption problem of the terrestrial solar spectrum and enhance broadband luminescence from a promising down conversion powder phosphor YPO4 co-doped with Pr3+-Yb3+ lanthanide ion-couple: incorporating a third sensitizing transition metal ion, e.g., Ti4+. The x-ray powder diffraction results confirm the lattice substitution by the solid-state reaction doping rather than the formation of any secondary phase. The emission spectral results and the luminescence decay curve analysis show that the downconversion luminescence can be enhanced by 200%–300% and the quantum efficiency enhanced by more than 20% at the wavelength of around 980 nm, the best response spectrum for Si-based solar cells, by optimizing TiO2 doping concentration at 7 mol. %.
Web tables have become very popular and important in many real applications, such as search engines and knowledge base enrichment. Due to its benefit, it is very urgent to understand web tables. An important task in web table understanding is the column-type detection, which detects the most likely types (categories) to describe the columns in the web table. Some existing studies use knowledge bases to determine the column types. However, this problem has three challenges. (i) Web tables are too dirty to be understood. (ii) Knowledge bases are not comprehensive enough to cover all the columns. (iii) The size of both knowledge bases and web tables are extremely huge. Thus, traditional approaches encounter the limitations with low quality and poor scalability. Also, they cannot extract the best type from top-k types automatically. To address these limitations, we propose a collective inference approach (CIA) based on Topic Sensitive PageRank, which considers not only the types of detected columns, but also the collective information of web tables to automatically produce more accurate top-k types, especially the top-1 type, for both incorrectly detected columns and undetectable columns whose cells do not exist in the knowledge base. We also propose three methods to improve the inference performance and implemented techniques of CIA in MapReduce. Experimental results on real-world datasets show that our CIA achieves much higher quality in top-1 type detection as well as the entity enrichment, and outperforms state-of-the-art approaches significantly.
To assess the effect of enteral nutrition (EN) supplemented with glutamine on recovery after ileal pouch-anal anastomosis (IPAA) in rats, to provide an experimental basis for nutritional support in patients with ulcerative colitis (UC) after IPAA.Male Sprague-Dawley (SD) rats were randomly divided into three groups (n = 8) after IPAA operation using a microsurgical technique. From the third postoperative day, rats in the control group, EN group, and immune nutrition (IN) group were fed standard rat chow, short peptide EN, and short peptide EN combined with glutamine ad libitum, respectively. The rats' general condition was observed throughout the study. Serum levels of total protein (TP), albumin (ALB), prealbumin (PA), and transferrin (TF) were detected on the 30th postoperative day, using an automatic biochemical analyzer. The ileal pouch mucosa was stained with hematoxylin and eosin (HE), and occludin protein levels were detected by immunohistochemistry.The body weight of rats in the EN group (359.20 ± 10.06 g) was significantly higher than that in the control group (344.00 ± 9.66 g) (P < 0.05) and lower than that in the IN group (373.60 ± 9.86 g) (P < 0.05) on the 30th postoperative day. The levels of serum TP, ALB, PA, and TF in the EN group were significantly higher than those in the control group (P < 0.01 for all) and lower than those in the IN group (P < 0.05 for all). Histopathological score (EN: 0.80 ± 0.37; IN: 0.60 ± 0.40; control group: 2.29 ± 0.18) and expression level of occludin protein (EN: 0.182 ± 0.054; IN: 0.188 ± 0.048; control group: 0.127 ± 0.032) were significantly lower in the control group compared with the EN and IN groups (P < 0.05 for all), but there were no significant differences between the latter two groups (P > 0.05 for all).EN combined with glutamine may effectively improve nutritional status after IPAA. Our results suggest a benefit of glutamine supplementation in EN for UC patients undergoing IPAA, although human studies are required to confirm this finding.
Two new bridging ligands have been synthesized by combining substituted benzaldehydes with phenanthrolinopyrrole (php), resulting in new polyazine bridging ligands. The ligands have been characterized by 1H NMR, mass spectroscopy, and elemental analysis. These new ligands display π–π* transitions above 500 nm with modest molar absorptivities. Upon excitation at the ligand-centered charge-transfer transition, weak emission with a maximum wavelength of 612 nm is observed. When coordinated to two ruthenium(II) bis(bipyridyl) groups, the new bimetallic complexes generated give an overall 4+ charge. The electronic transitions of the bimetallic ruthenium(II) complexes display traditional π–π* transitions at 287 nm and metal-to-ligand charge-transfer transitions at 452 nm with molar absorptivities greater than 30000 M–1 cm–1. Oxidation of the ruthenium(II) metal centers to ruthenium(III) occurs at potentials above 1.4 V versus the Ag/AgCl reference electrode. Spectroscopic and electrochemical measurements indicate that the ruthenium(II) moieties behave independently. Both complexes are water-soluble and show the ability to photonick plasmid DNA when irradiated with low-energy light above 550 nm. In addition, one of the complexes, [Ru(bpy)2php]2Van4+, shows the ability to linearize plasmid DNA and gives evidence, by gel electrophoresis, of photoinduced binding to plasmid DNA.
Data labelling is very important in many database and machine learning applications. Traditional methods rely on humans (workers or experts) to acquire labels. However, the human cost is rather expensive for a large dataset. Active learning based methods only label a small set of data with large uncertainty, train a model on these labelled data, and use the trained model to label the remainder unlabelled data. However they have two limitations. First, they cannot judiciously select appropriate data (task selection) and assign the tasks to proper humans (task assignment). Moreover, they independently process task selection and task assignment, which cannot capture the correlation between them. Second, they simply infer the truth of a task based on the answers from humans and the trained model (truth inference) by independently modeling humans and models. In other words, they ignore the correlation between them (the labelled data may have noise caused by humans with biases, and the model trained by the noisy labels may bring additional biases), and thus lead to poor inference results. To address these limitations, in this paper, we propose CrowdRL, an end-to-end reinforcement learning (RL) based framework for data labelling. To the best of our knowledge, CrowdRL is the first RL framework designed for the data labelling workflow by seamlessly integrating task selection, task assignment and truth inference together. CrowdRL fully utilizes the power of heterogeneous annotators (experts and crowdsourcing workers) and machine learning models together to infer the truth, which highly improves the quality of data labelling. CrowdRL uses RL to model task assignment and task selection, and designs an agent to judiciously assign tasks to appropriate workers. CrowdRL jointly models the answers of workers, experts and models, and designs a joint inference model to infer the truths. Experimental results on real datasets show that CrowdRL outperforms state-of-the-art approaches with the same (even fewer) monetary cost while achieving 5%-20% higher accuracy.
Two fusidane-type active compounds (6 and 7) and five new ones (1-5), along with other nine known compounds (8-16) were isolated from the metabolites of Schizophyllum commune MST7-3. Their structures were elucidated on the basis of spectroscopic analysis. The absolute configurations of compounds 2 and 3 were established by Mosher's method and optical rotation. Compounds 6 and 7 showed significant antibacterial activities against Stenotrophomonas maltophilia with MIC values of 4 μg/mL and 16 μg/mL, respectively.
The high efficient antireflective down-conversion Y2O3:Bi,Yb films with nano-structure pyramids were grown successfully on Si (100) substrates using the pulsed laser deposition (PLD). The films microstructure can be controllably tuned only by changing the oxygen pressure in PLD process. With the increasing of the oxygen pressure, the surface morphology changes from smooth surface to pyramid nano-structure, and the preferential orientation of films changes from (222) to (400). Besides, the average reflectance of the films decreases first and then increases, giving a minimum value of 15.8% at 5 Pa as the oxygen pressure increases, which is comparable to that of uniform pyramidal micro-textured surfaces with an average reflectance of 13%–15% fabricated by the complicated chemical etching method. Moreover, upon excitation of ultraviolet photon varying from 300 to 400 nm, near infrared emission of Yb3+ due to transition of the 2F5/2→2F7/2 was observed for all samples, which can be efficiently absorbed by silicon solar cell. These pyramid nano-structure down-conversion Y2O3:Bi,Yb films possess promising applications in enhancement of energy efficiency for crystalline Si solar cells by light trapping and spectrum shifting.