The outbreak of COVID-19 caused by SARS-CoV-2 has resulted in more than 50 million confirmed cases and over 1 million deaths worldwide as of November 2020. Currently, there are no effective ...antivirals approved by the Food and Drug Administration to contain this pandemic except the antiviral agent remdesivir. In addition, the trimeric spike protein on the viral surface is highly glycosylated and almost 200,000 variants with mutations at more than 1,000 positions in its 1,273 amino acid sequence were reported, posing a major challenge in the development of antibodies and vaccines. It is therefore urgently needed to have alternative and timely treatments for the disease. In this study, we used a cell-based infection assay to screen more than 3,000 agents used in humans and animals, including 2,855 small molecules and 190 traditional herbal medicines, and identified 15 active small molecules in concentrations ranging from 0.1 nM to 50 μM. Two enzymatic assays, along with molecular modeling, were then developed to confirm those targeting the virus 3CL protease and the RNA-dependent RNA polymerase. Several water extracts of herbal medicines were active in the cell-based assay and could be further developed as plant-derived anti-SARS-CoV-2 agents. Some of the active compounds identified in the screen were further tested in vivo, and it was found that mefloquine, nelfinavir, and extracts of
(RF3),
, and
were effective in a challenge study using hamsters as disease model.
The programmable one-pot oligosaccharide synthesis method was designed to enable the rapid synthesis of a large number of oligosaccharides, using the software Optimer to search Building BLocks (BBLs) ...with defined relative reactivity values (RRVs) to be used sequentially in the one-pot reaction. However, there were only about 50 BBLs with measured RRVs in the original library and the method could only synthesize small oligosaccharides due to the RRV ordering requirement. Here, we increase the library to include 154 validated BBLs and more than 50,000 virtual BBLs with predicted RRVs by machine learning. We also develop the software Auto-CHO to accommodate more data handling and support hierarchical one-pot synthesis using fragments as BBLs generated by the one-pot synthesis. This advanced programmable one-pot method provides potential synthetic solutions for complex glycans with four successful examples demonstrated in this work.
Lung cancer is the most commonly diagnosed cancer worldwide, and metastasis in lung cancer is the leading cause of cancer‐related deaths. Thus, understanding the mechanism of lung cancer metastasis ...will improve the diagnosis and treatment of lung cancer patients. Herein, we found that expression of cluster of differentiation 109 (CD109) was correlated with the invasive and metastatic capacities of lung adenocarcinoma cells. CD109 is upregulated in tumorous tissues, and CD109 overexpression was associated with tumor progression, distant metastasis, and a poor prognosis in patient with lung adenocarcinoma. Mechanistically, expression of CD109 regulates protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling via its association with the epidermal growth factor receptor (EGFR). Inhibition of CD109 decreases EGFR phosphorylation, diminishes EGF‐elicited activation of AKT/mTOR, and sensitizes tumor cells to an EGFR inhibitor. Taken together, our results show that CD109 is a potential diagnostic and therapeutic target in lung cancer patients.
CD109 promotes lung cancer metastasis through promoting EGFR‐AKT‐mTOR signaling and CD109 is an independent prognostic marker for lung adenocarcinoma.
A key challenge facing acquirers is how to judge the technological and other resources of high‐tech ventures. While it is well known that acquirers can benefit from signals about targets to reduce ...acquirers’ uncertainty in the selection of acquisition targets, this leaves open the question of the degree to which certain acquirers would rely on a target’s signals. We argue that different levels and types of experience can shape an acquirer’s attention to high‐tech ventures’ signals. On the one hand, general acquisition experience can lead an acquirer to pay more attention to and act on signals. On the other hand, target‐specific experience developed from prior collaborations can reduce the value of signals by directly mitigating an acquirer’s risk of adverse selection. Based on a sample of over a thousand technology ventures in the US biotechnology industry, our empirical evidence demonstrates that the combination of acquirers’ experiences and targets’ signals explains who buys whom in a high‐tech industry.
A planar metalens for achieving super‐resolution imaging in far‐field is proposed. This metalens, which has a non‐sub‐wavelength feature size, can be fabricated by conventional laser pattern ...generator. The imaging process is purely physical and captured in real time, without any pre‐ and post‐processing.
Efficient Algorithms for Mining Top-K High Utility Itemsets Tseng, Vincent S.; Cheng-Wei Wu; Fournier-Viger, Philippe ...
IEEE transactions on knowledge and data engineering,
2016-Jan.-1, 2016-1-1, Letnik:
28, Številka:
1
Journal Article
Recenzirano
High utility itemsets (HUIs) mining is an emerging topic in data mining, which refers to discovering all itemsets having a utility meeting a user-specified minimum utility threshold min_util. ...However, setting min_util appropriately is a difficult problem for users. Generally speaking, finding an appropriate minimum utility threshold by trial and error is a tedious process for users. If min_util is set too low, too many HUIs will be generated, which may cause the mining process to be very inefficient. On the other hand, if min_util is set too high, it is likely that no HUIs will be found. In this paper, we address the above issues by proposing a new framework for top-k high utility itemset mining, where k is the desired number of HUIs to be mined. Two types of efficient algorithms named TKU (mining Top-K Utility itemsets) and TKO (mining Top-K utility itemsets in One phase) are proposed for mining such itemsets without the need to set min_util. We provide a structural comparison of the two algorithms with discussions on their advantages and limitations. Empirical evaluations on both real and synthetic datasets show that the performance of the proposed algorithms is close to that of the optimal case of state-of-the-art utility mining algorithms.
•The multilayer hydrogel capsules are inspired by the unique features of onion.•The multilayer hydrogel capsules can avoid the burst release of DOX.•The multilayer hydrogel capsules are ...pH-sensitive.•The multilayer hydrogel capsules demonstrate good biocompatibility to HaCaT cells.
Inspired by the multilayer structure of onion, herein, a novel strategy to prepare bionic multilayer hydrogel capsules for inhibiting burst release of doxorubicin (DOX) is reported. The bionic multilayer hydrogel capsules are prepared by the ionotropic crosslinking method. Compared with monolayer hydrogel capsules, the multilayer hydrogel capsules can largely homogenize the distribution of DOX and suppress the concentration gradient of DOX between the outermost hydrogel layer and external environment and the dense cuticular membranes of capsules can restrict the migration and diffusion of DOX. As a result, a significant inhibition of the burst release of DOX can be achieved. Moreover, the bionic multilayer hydrogel capsules demonstrate pH sensitivity and good biocompatibility to human epidermal keratinocyte (HaCaT) cells. This work opens up a new horizon in the burst release of biomaterial-based hydrogels for drug delivery system.
Computational meta-optics brings a twist on the accelerating hardware with the benefits of ultrafast speed, ultra-low power consumption, and parallel information processing in versatile applications. ...Recent advent of metasurfaces have enabled the full manipulation of electromagnetic waves within subwavelength scales, promising the multifunctional, high-throughput, compact and flat optical processors. In this trend, metasurfaces with nonlocality or multi-layer structures are proposed to perform analog optical computations based on Green's function or Fourier transform, intrinsically constrained by limited operations or large footprints/volume. Here, we showcase a Fourier-based metaprocessor to impart customized highly flexible transfer functions for analog computing upon our single-layer Huygens' metasurface. Basic mathematical operations, including differentiation and cross-correlation, are performed by directly modulating complex wavefronts in spatial Fourier domain, facilitating edge detection and pattern recognition of various image processing. Our work substantiates an ultracompact and powerful kernel processor, which could find important applications for optical analog computing and image processing.
The Integrator is a multi-subunit protein complex that catalyzes the maturation of snRNA transcripts via 3' cleavage, a step required for snRNA incorporation with snRNP for spliceosome biogenesis. ...Here we developed a GFP based in vivo snRNA misprocessing reporter as a readout of Integrator function and performed a genome-wide RNAi screen for Integrator regulators. We found that loss of the Argonaute encoding csr-1 gene resulted in widespread 3' misprocessing of snRNA transcripts that is accompanied by a significant increase in alternative splicing. Loss of the csr-1 gene down-regulates the germline expression of Integrator subunits 4 and 6 and is accompanied by a reduced protein translation efficiency of multiple Integrator catalytic and non-catalytic subunits. Through isoform and motif mutant analysis, we determined that CSR-1's effect on snRNA processing is dependent on its catalytic slicer activity but does not involve the CSR-1a isoform. Moreover, mRNA-sequencing revealed high similarity in the transcriptome profile between csr-1 and Integrator subunit knockdown via RNAi. Together, our findings reveal CSR-1 as a new regulator of the Integrator complex and implicate a novel role of this Argonaute protein in snRNA 3' processing.
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