A new treatment for neurogenic inflammation caused by EV71 with CR2-targeted complement inhibitor

BACKGROUND: Enterovirus 71 (EV71), one of the most important neurotropic EVs, has caused death and long-term neurological sequelae in hundreds of thousands of young children in the Asia-Pacific region in the past decade. The neurological diseases are attributed to infection by EV71 inducing an extensive peripheral and central nervous system (CNS) inflammatory response with abnormal cytokine production and lymphocyte depletion induced by EV71 infection. In the absence of specific antiviral agents or vaccines, an effective immunosuppressive strategy would be valuable to alleviate the severity of the local inflammation induced by EV71 infection. PRESENTATION OF THE HYPOTHESIS: The complement system plays a pivotal role in the inflammatory response. Inappropriate or excessive activation of the complement system results in a severe inflammatory reaction or numerous pathological injuries. Previous studies have revealed that EV71 infection can induce complement activation and an inflammatory response of the CNS. CR2-targeted complement inhibition has been proved to be a potential therapeutic strategy for many diseases, such as influenza virus-induced lung tissue injury, postischemic cerebral injury and spinal cord injury. In this paper, a mouse model is proposed to test whether a recombinant fusion protein consisting of CR2 and a region of Crry (CR2-Crry) is able to specifically inhibit the local complement activation induced by EV71 infection, and to observe whether this treatment strategy can alleviate or even cure the neurogenic inflammation. TESTING THE HYPOTHESIS: CR2-Crry is expressed in CHO cells, and its biological activity is determined by complement inhibition assays. 7-day-old ICR mice are inoculated intracranially with EV71 to duplicate the neurological symptoms. The mice are then divided into two groups, in one of which the mice are treated with CR2-Crry targeted complement inhibitor, and in the other with phosphate-buffered saline. A group of mice deficient in complement C3, the breakdown products of which bind to CR2, are also infected with EV71 virus. The potential bioavailability and efficacy of the targeted complement inhibitor are evaluated by histology, immunofluorescence staining and radiolabeling. IMPLICATIONS OF THE HYPOTHESIS: CR2-Crry-mediated targeting complement inhibition will alleviate the local inflammation and provide an effective treatment for the severe neurological diseases associated with EV71 infection

The transport properties of Kekul\'e-ordered graphene pp-nn junctions

The transport properties of electrons in graphene $p$-$n$ junction with uniform Kekul\'e lattice distortion have been studied using the tight-binding model and the Landauer-B\"uttiker formalism combined with the nonequilibrium Green's function method. In the Kekul\'e-ordered graphene, the original $K$ and $K^{\prime}$ valleys of the pristine graphene are folded together due to the $\sqrt{3} \times \sqrt{3}$ enlargement of the primitive cell. When the valley coupling breaks the chiral symmetry, special transport properties of Dirac electrons exist in the Kekul\'e lattice. In the O-shaped Kekul\'e graphene $p$-$n$ junction, Klein tunneling is suppressed, and only resonance tunneling occurs. In the Y-shaped Kekul\'e graphene $p$-$n$ junction, the transport of electrons is dominated by Klein tunneling. When the on-site energy modification is introduced into the Y-shaped Kekul\'e structure, both Klein tunneling and resonance tunneling occur, and the electron tunneling is enhanced. In the presence of a strong magnetic field, the conductance of O-shaped and on-site energy-modified Y-shaped Kekul\'e graphene $p$-$n$ junctions is non-zero due to the occurrence of resonance tunneling. It is also found that the disorder can enhance conductance, with conductance plateaus forming in the appropriate range of disorder strength. The ideal plateau value is found only in the Kekul\'e-Y system.Comment: 8 pages, 7 figure

A map of human cancer signaling

We conducted a comprehensive analysis of a manually curated human signaling network containing 1634 nodes and 5089 signaling regulatory relations by integrating cancer-associated genetically and epigenetically altered genes. We find that cancer mutated genes are enriched in positive signaling regulatory loops, whereas the cancer-associated methylated genes are enriched in negative signaling regulatory loops. We further characterized an overall picture of the cancer-signaling architectural and functional organization. From the network, we extracted an oncogene-signaling map, which contains 326 nodes, 892 links and the interconnections of mutated and methylated genes. The map can be decomposed into 12 topological regions or oncogene-signaling blocks, including a few ‘oncogene-signaling-dependent blocks' in which frequently used oncogene-signaling events are enriched. One such block, in which the genes are highly mutated and methylated, appears in most tumors and thus plays a central role in cancer signaling. Functional collaborations between two oncogene-signaling-dependent blocks occur in most tumors, although breast and lung tumors exhibit more complex collaborative patterns between multiple blocks than other cancer types. Benchmarking two data sets derived from systematic screening of mutations in tumors further reinforced our findings that, although the mutations are tremendously diverse and complex at the gene level, clear patterns of oncogene-signaling collaborations emerge recurrently at the network level. Finally, the mutated genes in the network could be used to discover novel cancer-associated genes and biomarkers

Balancing dynamic evolution of active sites for urea oxidation in practical scenarios

Electrochemical urea splitting provides a sustainable and environmentally benign route for facilitating energy conversion. Nonetheless, the sustained efficiency of urea splitting is impeded by a scarcity of active sites during extended operational periods. Herein, an atomic heterostructure engineering strategy is proposed to promote the generation of active species via synthesizing unique Ru–O4 coordinated single atom catalysts anchored on Ni hydroxide (Ru1–Ni(OH)2), with ultralow Ru loading mass of 40.6 μg cm−2 on the nickel foam for commercial feasibility. Leveraging in situ spectroscopic characterizations, the structure-performance relationship in low and high urea concentrations was investigated and exhibited extensive universality. The boosted generation of dynamic Ni3+ active sites ensures outstanding activity and prominent long-term durability tests in various practical scenarios, including 100 h Zn–urea–air battery operation, 100 h alkaline urine electrolysis, and over 400 h stable hydrogen production in membrane electrode assembly (MEA) system under industrial-level current density

DeepDyve: Dynamic Verification for Deep Neural Networks

Deep neural networks (DNNs) have become one of the enabling technologies in many safety-critical applications, e.g., autonomous driving and medical image analysis. DNN systems, however, suffer from various kinds of threats, such as adversarial example attacks and fault injection attacks. While there are many defense methods proposed against maliciously crafted inputs, solutions against faults presented in the DNN system itself (e.g., parameters and calculations) are far less explored. In this paper, we develop a novel lightweight fault-tolerant solution for DNN-based systems, namely DeepDyve, which employs pre-trained neural networks that are far simpler and smaller than the original DNN for dynamic verification. The key to enabling such lightweight checking is that the smaller neural network only needs to produce approximate results for the initial task without sacrificing fault coverage much. We develop efficient and effective architecture and task exploration techniques to achieve optimized risk/overhead trade-off in DeepDyve. Experimental results show that DeepDyve can reduce 90% of the risks at around 10% overhead