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Most α2-AR agonists derived from dexmedetomidine have few structural differences between them and have no selectivity for α2A/2B-AR or Gi/Gs, which can lead to side effects in drugs. To obtain novel and potent α2A-AR agonists, we performed virtual screening for human α2A-AR and α2B-AR to find α2A-AR agonists with higher selectivity. Compound P300–2342 and its three analogs significantly decreased the locomotor activity of mice (p < 0.05). Furthermore, P300–2342 and its three analogs inhibited the binding of [3H] Rauwolscine with IC50 values of 7.72 ± 0.76 and 12.23 ± 0.11 μM, respectively, to α2A-AR and α2B-AR. In α2A-AR-HEK293 cells, P300–2342 decreased forskolin-stimulated cAMP production without increasing cAMP production, which indicated that P300–2342 activated α2A-AR with coupling to the Gαi/o pathway but without Gαs coupling. P300–2342 exhibited no agonist but slight antagonist activities in α2B-AR. Similar results were obtained for the analogs of P300–2342. The docking results showed that P300–2342 formed π-hydrogen bonds with Y394, V114 in α2A-AR, and V93 in α2B-AR. Three analogs of P300–2342 formed several π-hydrogen bonds with V114, Y196, F390 in α2A-AR, and V93 in α2B-AR. We believe that these molecules can serve as leads for the further optimization of α2A-AR agonists with potentially few side effects. [ABSTRACT FROM AUTHOR]

Based on panel data for 30 provinces in China from 2000 to 2020, this paper uses entropy method to construct the integrated development indicators of energy Internet, and explores the impact of the development of the energy Internet on reducing carbon emissions in China and its internal transmission mechanism. The research results show that the development of energy Internet can significantly reduce regional carbon dioxide emissions, and increasing the use of renewable energy is an important mechanism for the comprehensive development of energy Internet to curb carbon emissions. Heterogeneity analysis shows that the emission reduction effect brought by the development of energy Internet is more remarkable in the regions with lower carbon emissions and western China. Furthermore, this paper finds that in the setting of the development of energy Internet, the development of renewable energy can promote natural gas consumption and advance energy conversion efficiency. The government's emphasis on regional technology development has an external strengthening effect on carbon emission reduction. The research in this paper expands and diversifies carbon reduction pathways and provides reference for more developing countries to utilize the development of energy internet to achieve carbon reduction. [ABSTRACT FROM AUTHOR]

This letter examines the impact of political uncertainty on stock prices by utilizing a quasi-experiment, i.e. Taiwan accidentally fires a missile towards mainland China. As this missile accident was entirely unforeseen by investors in the market, it provided a complete exogenous shock causing political uncertainty. We find that the political uncertainty caused by the events has significant negative effects on stock prices, especially for firms that have economic and geographical connections with Taiwan or are adjacent to Taiwan. [ABSTRACT FROM AUTHOR]

As the problem of carbon emissions is becoming increasingly more serious around the world, how to balance carbon emissions reduction and economic growth has become an important issue in the field of environmental economics. China is the world's largest carbon dioxide emitter, and China's Low-Carbon Pilot (CLCP) policy has significantly reduced carbon dioxide emissions and achieved expected benefits. However, is environmental quality improving at the expense of economic growth? This article selects macro panel data of 286 Chinese prefecturelevel cities and micro data of Chinese industrial enterprises from 2001 to 2013, takes the CLCP policy implementation by five provinces and eight cities as a quasi-natural experiment, uses difference-in-differences (DID) method to investigate the causal effect of CLCP policy on regional economic growth and enterprise behavior. The results are as follows. First, the CLCP policy significantly promotes regional economic growth. Moreover, as the implementation time of the policy continues, environmental regulation has a greater effect of promoting economic growth. Second, although the CLCP policy significantly increases various production costs, it also promotes the growth of enterprises' output and benefits. Third, under the pressure of enterprise cost increase caused by environmental regulation, enterprises choose the positive way of strengthening internal management, improving efficiency and increasing innovation instead of choosing the negative way of trans-regional transfer, and finally achieve an improvement in output and benefits.

The clinical course of myasthenia gravis (MG) during pregnancy is highly variable and unpredictable. The management of MG in pregnancy has not been standardized.