Atopic dermatitis is a chronic, relapsing form of inflammatory skin disorder that is affected by genetic and environmental factors. We performed a genome-wide association study of atopic dermatitis in a Chinese Han population using 1,012 affected individuals (cases) and 1,362 controls followed by a replication study in an additional 3,624 cases and 12,197 controls of Chinese Han ethnicity, as well as 1,806 cases and 3,256 controls from Germany. We identified previously undescribed susceptibility loci at 5q22.1 (TMEM232 and SLC25A46, rs7701890, P(combined) = 3.15 × 10(-9), odds ratio (OR) = 1.24) and 20q13.33 (TNFRSF6B and ZGPAT, rs6010620, P(combined) = 3.0 × 10(-8), OR = 1.17) and replicated another previously reported locus at 1q21.3 (FLG, rs3126085, P(combined) = 5.90 × 10(-12), OR = 0.82) in the Chinese sample. The 20q13.33 locus also showed evidence for association in the German sample (rs6010620, P = 2.87 × 10(-5), OR = 1.25). Our study identifies new genetic susceptibility factors and suggests previously unidentified biological pathways in atopic dermatitis.

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Environmental regulation is an important driving force of green technology innovation. In this paper, environmental policy instruments are classified into three categories: command-control, market-incentive and social-will. Based on the panel data of 30 provinces in China from 2010 to 2017, a fixed effect model and a panel threshold regression model are used to test the heterogeneous effects of different types of environmental policy instruments on the green technology innovation in China. The results show that: (1) Overall, China’s environmental policy instruments do not provide sufficient impetus for green technology innovation; (2) The impact of command-control environmental policy instruments on green technology innovation has a single threshold effect. When its intensity exceeds a certain threshold, green technology innovation is improved. The impact of market-incentive environmental policy instruments on the green technology innovation shows a double threshold effect, that is to say, only when its intensity maintained within a reasonable interval, can green technology innovation be promoted by it; (3) There is significant spatial difference in the impact of different types of environmental policy instruments on green technology innovation. In order to induce green technology innovation, it is necessary to formulate a combined and differentiated environmental policy system, while rationally adjusting the strength of different types of environmental policy instruments.

An improved control strategy for the three-phase grid-connected inverter with space vector pulse width modulation (SVPWM) is proposed. When the grid current contains harmonics, the d-and q-axis grid currents will be interacted, and then the waveform quality of the grid current will be poorer. As the reference output voltage cannot directly reflect the change of the reference grid current, the dynamic response of the grid-connected inverter is slow. In order to solve the aforementioned problems, the d-and q-axis grid currents in the decoupled components of the grid current controller can be substituted by the d-and q-axis reference grid currents, respectively. The operating principles of the traditional and proposed control methods are illustrated. Experimental results for a 15-kVA three-phase grid-connected inverter with SVPWM verify the theoretical analysis. Compared with the traditional control strategy, the grid-connected inverter with the improved control strategy has high waveform quality of the grid current, small ripple power, and fast dynamic response.

A series of novel benzo [c][1,2,5]oxadiazole derivatives were designed, synthesized, and biologically evaluated as inhibitors of PD-L1. Among them, compound L7 exhibited 1.8 nM IC 50 value in a homogeneous time-resolved fluorescence (HTRF) assay, which was 20-fold more potent than the lead compound BMS-1016. In the surface plasmon resonance (SPR) assay, L7 bound to human PD-L1 (hPD-L1) with a K D value of 3.34 nM, without showing any binding to hPD-1. In the cell-based coculture assay, L7 blocked PD-1/PD-L1 interaction with an EC 50 value of 375 nM, while BMS-1016 had an EC 50 value of 2075 nM. Moreover, compound L24, an ester prodrug of L7, was orally bioavailable and displayed significant antitumor effects in tumor models of syngeneic and PD-L1 humanized mice. Mechanistically, L24 exhibited significant in vivo antitumor effects probably through promoting antitumor immunity. Together, this series of benzoxadiazole PD-L1 inhibitors holds promise for tumor immunotherapy. Preclinical trials with selected compounds are ongoing in our laboratory.