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CD4 + T cells have numerous features of over-activated cellular metabolism in lupus patients and mouse models of the disease. This includes a higher glycolysis than in healthy controls. Glucose transporters play an essential role in glucose metabolism by controlling glucose import into the cell from the extracellular environment. We have previously shown that treatment of lupus-prone mice with 2-deoxy-D-glucose, which inhibits the first step of glycolysis was sufficient to prevent autoimmune activation. However, direct targeting of glucose transporters has never been tested in a mouse model of lupus. Here, we show that CG-5, a novel glucose transporter inhibitor, ameliorated autoimmune phenotypes in a spontaneous lupus-prone mouse model, B6.NZM2410. Sle1.Sle2.Sle3 (Triple-congenic, TC), and in a chronic graft- vs. host-disease (cGVHD) model of induced lupus. In vitro , CG-5 blocked glycolysis in CD4 + T cells, and limited the expansion of CD4 + T cells induced by alloreactive stimulation. CG-5 also modulated CD4 + T cell polarization by inhibiting Th1 and Th17 differentiation and promoting regulatory T (Treg) induction. Moreover, CG-5 treatment reduced lupus phenotypes including the expansion of germinal center B (GC B) cells, as well as the production of autoantibodies in both TC mice and cGVHD models. Finally, CG-5 blocked glycolysis in human T cells. Overall, our data suggest that blocking glucose uptake with a small molecule inhibitor ameliorates autoimmune activation, at least partially due to its inhibition of glycolysis in CD4 + T cells.

A new type of flexible proximity sensor that uses a microsized organic crystal as the sensing element is demonstrated. The two-terminal organic sensor can accurately perceive the external objects, such as the human finger, fiber, and even atomic force microscopy tip. The proximity sensor shows an unprecedented distance resolution of 0.05 mm, which is 2 orders of magnitude higher than that of the previously reported conventional capacitor proximity sensors. A novel method has been proposed to realize the location detection of the approaching unknown-charge object by changing the distance between the stimulus and the sensor. Our results open a new route to realize an ultrasensitive perception of objects, making it a promising candidate for applications in artificial intelligence, healthcare systems, and high-precision robots.

Bioelectronics in synaptic transistors for future biomedical applications, such as implanted treatments and human-machine interfaces, must be flexible with good mechanical compatibility with biological tissues. The rigid nature and high deposition temperature in conventional inorganic synaptic transistors restrict the development of flexible, conformal synaptic devices. Here, the dinaphtho[2,3-b:2′,3′-f ]thieno[3,2-b]-thiophene organic synaptic transistor on elastic polydimethylsiloxane is demonstrated to avoid these limitations. The unique advantages of organic materials in low Young's modulus and low temperature process enable seamless adherence of organic synaptic transistors on arbitrary-shaped objects. On 3D curved surfaces, the essential synaptic functions, such as potentiation/depression, short/long-term synaptic plasticity, and spike voltage-dependent plasticity, are successfully realized. The time-dependent surface potential characterization reveals the slow polarization of dipoles in the dielectric is responsible for hysteresis and synaptic behaviors. This work represents that organic materials offer a potential platform to realize the flexible, conformal synaptic transistors for the development of wearable and implantable artificial neuromorphic systems.

Abstract:In this paper, we present surface urban heat island (SUHI) analysis of Shanghai (China) based on the change in land use and land cover using satellite Landsat images from 2002 to 2013. With the rapid development of urbanization, urban ecological and environmental issues have aroused widespread concern. The urban heat island (UHI) effect is a crucial problem, as its generation and evolution are closely related to social and economic activities. Land-use and land-cover change (LUCC) is the key in analyzing the UHI effect. Shanghai, one of China's major economic, financial and commercial centers, has experienced high development density for several decades. A tremendous amount of farmland and vegetation coverage has been replaced by an urban impervious surface, leading to an intensive SUHI effect, especially in the city's center. Luckily, the SUHI trend has slowed due to reasonable urban planning and relevant green policies since the 2010 Expo. Data analyses demonstrate that an impervious surface (IS) has a positive correlation with land surface temperature (LST) but a negative correlation with vegetation and water. Among the three factors, impervious surface is the most relevant. Therefore, the policy implications of land use and control of impervious surfaces should pay attention to the relief of the current SUHI effect in Shanghai.Keywords: surface urban heat island (SUHI); land-use and land-cover change (LUCC); land surface temperature (LST); Shanghai; NDVI; MNDWI

Z-DNA, a left-handed duplex, has been shown to form in vivo and regulate expression of the corresponding gene. However, its biological roles have not been satisfactorily understood, mainly because Z-DNA is easily converted to the thermodynamically favorable B-DNA. Here we present a new idea to form stable Z-DNA under normal physiological conditions and achieve detailed analysis on its fundamental features. Simply by mixing two complementary minicircles of single-stranded DNA with no chemical modification, the hybridization spontaneously induces topological constraint which twines one-half of the double-stranded DNA into stable Z-DNA. The formation of Z-conformation with high stability has been proved by using circular dichroism spectroscopy, Z-DNAspecific antibody binding assay, nuclease digestion, etc. Even at a concentration of MgCl 2 as low as 0.5 mM, Z-DNA was successfully obtained, avoiding the use of high salt conditions, limited sequences, ancillary additives, or chemical modifications, criteria which have hampered Z-DNA research. The resultant Z-DNA has the potential to be used as a canonical standard sample in Z-DNA research. By using this approach, further developments of Z-DNA science and its applications become highly promising.

Fraxetin is one of the main constituents of the traditional medicinal plant Fraxinus rhynchophylla. The inhibitory effect of fraxetin on various bacterial strains has been extensively reported, however, its mechanism of action on bacterial cells remains to be elucidated. In the present study, the antibacterial mechanism of fraxetin on Staphylococcus aureus was systematically investigated by examining its effect on cell membranes, protein synthesis, nucleic acid content and topoisomerase activity. The results indicated that fraxetin increased the permeability of the cell membrane but did not render it permeable to macromolecules, such as DNA and RNA. Additionally, the quantity of protein, DNA and RNA decreased to 55.74, 33.86 and 48.96%, respectively following treatment with fraxetin for 16 h. The activity of topoisomerase I and topoisomerase II were also markedly inhibited as fraxetin concentration increased. The result of the ultraviolet-visible spectrophotometry demonstrated that the DNA characteristics exhibited a blue shift and hypochromic effect following treatment with fraxetin. These results indicated that fraxetin had a marked inhibitory effect on S.aureus proliferation. Further mechanistic studies showed that fraxetin could disrupt nucleic acid and protein synthesis by preventing topoisomerase from binding to DNA.

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