Supramolecular Aptamers on Graphene Oxide for Efficient Inhibition of Thrombin Activity

Graphene oxide (GO), a two-dimensional material with a high aspect ratio and polar functional groups, can physically adsorb single-strand DNA through different types of interactions, such as hydrogen bonding and π-π stacking, making it an attractive nanocarrier for nucleic acids. In this work, we demonstrate a strategy to target exosites I and II of thrombin simultaneously by using programmed hybrid-aptamers for enhanced anticoagulation efficiency and stability. The targeting ligand is denoted as Supra-TBA15/29 (supramolecular TBA15/29), containing TBA15 (a 15-base nucleotide, targeting exosite I of thrombin) and TBA29 (a 29-base nucleotide, targeting exosite II of thrombin), and it is designed to allow consecutive hybridization of TBA15 and TBA29 to form a network of TBAs (i.e., supra-TBA15/29). The programmed hybrid-aptamers (Supra-TBA15/29) were self-assembled on GO to further boost anticoagulation activity by inhibiting thrombin activity, and thus suppress the thrombin-induced fibrin formation from fibrinogen. The Supra-TBA15/29-GO composite was formed mainly through multivalent interaction between poly(adenine) from Supra-TBA15/29 and GO. We controlled the assembly of Supra-TBA15/29 on GO by regulating the preparation temperature and the concentration ratio of Supra-TBA15/29 to GO to optimize the distance between TBA15 and TBA29 units, aptamer density, and aptamer orientation on the GO surfaces. The dose-dependent thrombin clotting time (TCT) delay caused by Supra-TBA15/29-GO was >10 times longer than that of common anticoagulant drugs including heparin, argatroban, hirudin, and warfarin. Supra-TBA15/29-GO exhibits high biocompatibility, which has been proved by in vitro cytotoxicity and hemolysis assays. In addition, the thromboelastography of whole-blood coagulation and rat-tail bleeding assays indicate the anticoagulation ability of Supra-TBA15/29-GO is superior to the most widely used anticoagulant (heparin). Our highly biocompatible Supra-TBA15/29-GO with strong multivalent interaction with thrombin [dissociation constant (Kd) = 1.9 × 10−11 M] shows great potential as an effective direct thrombin inhibitor for the treatment of hemostatic disorders

Towards Long-Tailed Recognition for Graph Classification via Collaborative Experts

Graph classification, aiming at learning the graph-level representations for effective class assignments, has received outstanding achievements, which heavily relies on high-quality datasets that have balanced class distribution. In fact, most real-world graph data naturally presents a long-tailed form, where the head classes occupy much more samples than the tail classes, it thus is essential to study the graph-level classification over long-tailed data while still remaining largely unexplored. However, most existing long-tailed learning methods in visions fail to jointly optimize the representation learning and classifier training, as well as neglect the mining of the hard-to-classify classes. Directly applying existing methods to graphs may lead to sub-optimal performance, since the model trained on graphs would be more sensitive to the long-tailed distribution due to the complex topological characteristics. Hence, in this paper, we propose a novel long-tailed graph-level classification framework via Collaborative Multi-expert Learning (CoMe) to tackle the problem. To equilibrate the contributions of head and tail classes, we first develop balanced contrastive learning from the view of representation learning, and then design an individual-expert classifier training based on hard class mining. In addition, we execute gated fusion and disentangled knowledge distillation among the multiple experts to promote the collaboration in a multi-expert framework. Comprehensive experiments are performed on seven widely-used benchmark datasets to demonstrate the superiority of our method CoMe over state-of-the-art baselines.Comment: Accepted by IEEE Transactions on Big Data (TBD 2024

The Known Distribution of an Invasive Lizard, the Brown Anole (Anolis sagrei Duméril & Bibron, 1837), in Taiwan

The Brown Anole (Anolis sagrei) has become an invasive species in some parts of the Americas and in some localities in the Pacific region. In Taiwan A. sagrei was recorded for the first time in 2000 in Santzepu, southwestern Taiwan, and was subsequently recorded in Chisintang, eastern Taiwan, during 2006. For future monitoring and research, we describe the known distribution of A. sagrei in Taiwan by plotting GPS coordinates of localities where A. sagrei was observed during surveys (conducted on an ad hoc basis since this species was first discovered in Taiwan) or where specimens have been collected on GIS User Community aerial photographs that were divided into 100 x 100-m grids. We recorded this invasive lizard in southwestern Taiwan in an area spanning approximately 237 ha and in an approximately 8-ha area in eastern Taiwan. Since A. sagrei is easily spread by human activities, and because not all areas could be thoroughly surveyed, we conclude that the current actual distribution of A. sagrei in Taiwan is probably more extensive than shown. We believe that the eradication of A. sagrei in Taiwan through removal is unrealistic, and propose that ongoing efforts should focus on managing this species

A Survey of Graph Neural Networks in Real world: Imbalance, Noise, Privacy and OOD Challenges

Graph-structured data exhibits universality and widespread applicability across diverse domains, such as social network analysis, biochemistry, financial fraud detection, and network security. Significant strides have been made in leveraging Graph Neural Networks (GNNs) to achieve remarkable success in these areas. However, in real-world scenarios, the training environment for models is often far from ideal, leading to substantial performance degradation of GNN models due to various unfavorable factors, including imbalance in data distribution, the presence of noise in erroneous data, privacy protection of sensitive information, and generalization capability for out-of-distribution (OOD) scenarios. To tackle these issues, substantial efforts have been devoted to improving the performance of GNN models in practical real-world scenarios, as well as enhancing their reliability and robustness. In this paper, we present a comprehensive survey that systematically reviews existing GNN models, focusing on solutions to the four mentioned real-world challenges including imbalance, noise, privacy, and OOD in practical scenarios that many existing reviews have not considered. Specifically, we first highlight the four key challenges faced by existing GNNs, paving the way for our exploration of real-world GNN models. Subsequently, we provide detailed discussions on these four aspects, dissecting how these solutions contribute to enhancing the reliability and robustness of GNN models. Last but not least, we outline promising directions and offer future perspectives in the field

Nuclear Export Signal Mutation of Epidermal Growth Factor Receptor Enhances Malignant Phenotypes of Cancer Cells

Nuclear epidermal growth factor receptor (EGFR) has been shown to be correlated with drug resistance and a poor prognosis in patients with cancer. Previously, we have identified a tripartite nuclear localization signal (NLS) within EGFR. To comprehensively determine the functions and underlying mechanism of nuclear EGFR and its clinical implications, we aimed to explore the nuclear export signal (NES) sequence of EGFR that is responsible for interacting with the exportins. We combined in silico prediction with site-directed mutagenesis approaches and identified a putative NES motif of EGFR, which is located in amino acid residues 736-749. Mutation at leucine 747 (L747) in the EGFR NES led to increased nuclear accumulation of the protein via a less efficient release of the exportin CRM1. Interestingly, L747 with serine (L747S) and with proline (L747P) mutations were found in both tyrosine kinase inhibitor (TKI)-treated and -naïve patients with lung cancer who had acquired or de novo TKI resistance and a poor outcome. Reconstituted expression of the single NES mutant EGF

Enhancing electron transport in molecular wires by insertion of a ferrocene center

National Natural Science Foundation of China [21003110, 21273204, 20803027, 21173094]We have determined the conductance of alkane-linked ferrocene molecules with carboxylic acid anchoring groups using the STM break junction technique, and three sets of conductance values were found, i.e. high conductance (HC), medium conductance (MC) and low conductance (LC) values. The enhancing effect of the incorporated ferrocene on the electron transport in saturated alkane molecular wires is demonstrated by the increased conductance of the ferrocene molecules, attributed to the reduction of the tunneling barrier and the HOMO-LUMO gap induced by the insertion of ferrocene. Furthermore, the electron-withdrawing carbonyl group on the unconjugated backbone has little or no influence on single-molecule conductance. The current work provides a feasible approach for the design of high-performance molecular wires

The CDEX-1 1 kg Point-Contact Germanium Detector for Low Mass Dark Matter Searches

The CDEX Collaboration has been established for direct detection of light dark matter particles, using ultra-low energy threshold p-type point-contact germanium detectors, in China JinPing underground Laboratory (CJPL). The first 1 kg point-contact germanium detector with a sub-keV energy threshold has been tested in a passive shielding system located in CJPL. The outputs from both the point-contact p+ electrode and the outside n+ electrode make it possible to scan the lower energy range of less than 1 keV and at the same time to detect the higher energy range up to 3 MeV. The outputs from both p+ and n+ electrode may also provide a more powerful method for signal discrimination for dark matter experiment. Some key parameters, including energy resolution, dead time, decay times of internal X-rays, and system stability, have been tested and measured. The results show that the 1 kg point-contact germanium detector, together with its shielding system and electronics, can run smoothly with good performances. This detector system will be deployed for dark matter search experiments.Comment: 6 pages, 8 figure

FAST observations of an extremely active episode of FRB 20201124A: III. Polarimetry

As the third paper in the multiple-part series, we report the statistical properties of radio bursts detected from the repeating fast radio burst (FRB) source FRB 20201124A with the Five-hundred-meter Aperture Spherical radio telescope (FAST) during an extremely active episode between the 25th and the 28th of September 2021 (UT). We focus on the polarisation properties of 536 bright bursts with $\mathrm{S/N}>50$. We found that the Faraday rotation measures (RMs) monotonically dropped from $-579 \ {\rm rad \ m^{-2}}$ to $-605 \ {\rm rad \ m^{-2}}$ in the 4-day window. The RM values were compatible with the values ($-300$ to $-900\ {\rm rad \ m^{-2}}$ ) reported 4 month ago (Xu et al. 2022). However, the RM evolution rate in the current observation window was at least an order of magnitude smaller than the one ($\sim 500\ {\rm rad \ m^{-2}\, day^{-1}}$) previously reported during the rapid RM-variation phase, but is still higher than the one ($\le 1\ {\rm rad \ m^{-2} day^{-1}}$) during the later RM no-evolution phase. The bursts of FRB 20201124A were highly polarised with the total degree of polarisation (circular plus linear) greater than 90polarisation position angles (PAs), degree of linear polarisation ($L/I$), and degree of circular polarisation ($V/I$) can be characterised with unimodal distribution functions. During the observation window, the distributions became wider with time, i.e. with larger scatter, but the centroids of the distribution functions remained nearly constant. For individual bursts, significant PA variations (confidence level 5-$\sigma$) were observed in 33% of all bursts. The polarisation of single pulses seems to follow certain complex trajectories on the Poincar\'e sphere, which may shed light on the radiation mechanism at the source or the plasma properties along the path of FRB propagation.Comment: 25 pages, 16 figures. Accepted by Research in Astronomy and Astrophysics (RAA