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Mutations in the KCNQ2 gene encoding KV7.2 subunit that mediates neuronal M-current cause a severe form of developmental and epileptic encephalopathy (DEE). Electrophysiological evaluation of KCNQ2 mutations has been proved clinically useful in improving outcome prediction and choosing rational anti-seizure medications (ASMs). In this study we described the clinical characteristics, electrophysiological phenotypes and the in vitro response to KCNQ openers of five KCNQ2 pore mutations (V250A, N258Y, H260P, A265T and G290S) from seven patients diagnosed with KCNQ2-DEE. The KCNQ2 variants were transfected into Chinese hamster ovary (CHO) cells alone, in combination with KCNQ3 (1:1) or with wild-type KCNQ2 (KCNQ2-WT) and KCNQ3 in a ratio of 1:1:2, respectively. Their expression and electrophysiological function were assessed. When transfected alone or in combination with KCNQ3, none of these mutations affected the membrane expression of KCNQ2, but most failed to induce a potassium current except A265T, in which trace currents were observed when co-transfected with KCNQ3. When co-expressed with KCNQ2-WT and KCNQ3 (1:1:2), the currents at 0 mV of these mutations were decreased by 30%-70% compared to the KCNQ2/3 channel, which could be significantly rescued by applying KCNQ openers including the approved antiepileptic drug retigabine (RTG, 10 μM), as well as two candidates subjected to clinical trials, pynegabine (HN37, 1 μM) and XEN1101 (1 μM). These newly identified pathologic variants enrich the KCNQ2-DEE mutation hotspots in the pore-forming domain. This electrophysiological study provides a rational basis for personalized therapy with KCNQ openers in DEE patients carrying loss-of-function (LOF) mutations in KCNQ2.

In order to explore which ecological strategies the remnant vegetation is taken to adapt to urbanization, we investigated three kinds of typical remnant vegetation (grassland, plantation, and secondary forest) in 16 sample sites along the urban–rural gradient in the city of Guangzhou. In this study, we examined plant species composition, and plant diversity, and analyzed the seed of the dominant tree species Schima superba (S. superba) in the secondary forest sites. Those indicators are strongly related with ecological strategies. Eighteen landscape pattern characteristics were determined to reveal the extent of landscape fragmentation. Geographic Information System (GIS), linear regression, and Canonical Correspondence Analysis (CCA) were conducted to analyze the influence of landscape pattern characteristics on plant communities. Results showed that (1) Fragmentation of landscape patterns caused by urbanization has a negative impact on the diversity of herb-layer plants, the dominant species of grassland in the city center are mainly weeds, such as Bidens pilosa and Neyraudia reynaudiana. (2) In order to adapt to the pressure of landscape fragmentation, seeds of S. superba have developed into a larger size, with a competitive advantage over smaller ones. (3) Two different ecological strategies of plant communities adapting to urbanization: The pioneer weeds in grasslands, with high reproductive and dispersal ability, have adopted a r-selection strategy and the dominant tree species with higher survival rates, larger individuals, and longer life spans, have adopted a K-selection strategy to resist disturbance, as well as with a larger seed size to increase viability and settlement ability.