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It remains a challenge for the effective treatment of neuroinflammatory disease, including multiple sclerosis (MS), stroke, epilepsy, and Alzheimer's and Parkinson's disease. The voltage-gated potassium Kv1.3 channel is of interest, which is considered as a novel therapeutic target for treating neuroinflammatory disorders due to its crucial role in subsets of T lymphocytes as well as microglial cells. Toxic animals, such as sea anemones, scorpions, spiders, snakes, and cone snails, can produce a variety of toxins that act on the Kv1.3 channel. The K channel blocking toxin (ShK) from the sea anemone is proved as a classical blocker of Kv1.3. One of the synthetic analogs ShK-186, being developed as a therapeutic for autoimmune diseases, has successfully completed first-in-man Phase 1 trials. In addition to addressing the recent progress on the studies underlying the pharmacological characterizations of ShK on MS, the review will also explore the possibility for clinical treatment of ShK-like Kv1.3 blocking polypeptides on other neuroinflammatory diseases.

Flexible perovskite photodetectors (FPDs) are promising for novel wearable devices in bionics, robotics and health care. However, their performance degradation and instability during operations remain a grand challenge. Superior flexibility and spontaneous functional repair of devices without the need for any external drive or intervention are ideal goals for FPDs. Herein, by using phenyl disulfide instead of alkyl disulfide as a crosslinking agent, disulfide bonds with lower bond energy are introduced, thus endowing the polyurethane network (SCPU) with the ability of self‐healing at room temperature. SCPU is filled to the grain boundary of perovskite film, which not only improves the crystal quality of perovskite and mechanical stability of FPD but also enables FPD to self‐heal at room temperature. As a result, the as‐prepared FPD exhibits a superior responsivity of 0.4 A W−1, a high specific detectivity of 2.5 × 1011 Jones and 2 μs fast response time in a self‐powered mode. More importantly, the FPD still retained 91% of the initial photo responsivity after 9000 times of bending upon cyclic healing. This polymer doping strategy provides an effective solution for stable operation and room‐temperature self‐healing for FPDs. Benzene rings can lower the recombination temperature of self‐healing groups in SCPU, achieving self‐healing at room temperature. When added to the flexible perovskite photodetector, the chemical bond crosslinking network in the SCPU can endow the device with self‐healing effect. The device still retained 91% of the initial photo responsivity after 9000 times of bending upon cyclic healing.

An urban flood simulation model based on TELEMAC-2D was constructed, and the inundation data of two measured rainstorms (7 June 2018 and 16 September 2018) were selected to validate the model. Flooding processes were simulated under 12 designed rainfall scenarios with rainfall return periods of 20, 50 and 100 years and rainfall peak coefficients of 0.2, 0.4, 0.6 and 0.8, respectively. The hazard-vulnerability (H-V) method was used for urban flood risk assessment. The selected hazard factors included inundation depth, flood velocity, elevation and slope. The vulnerability factors included land use type, population density and property distribution. The analytic hierarchy process (AHP) method was used to calculate the weight values of each indicator factor, and ArcGIS software was used for overlay calculation. The results of the analysis show that as the rainfall peak coefficient factor increases, the area of each risk zone increases to varying degrees. The larger the rainfall peak coefficient factor, the more serious the flooding. As the rainfall return period increases, the effect of the rainfall peak coefficient factor of the change in the area of the highest risk zone diminishes. The highest risk zone is the largest within Luohu District (LHD), accounting for 46.38%, 60.92% and 45.54% of the total highest risk area, respectively. As the return period increases, the area of the highest risk zone within Futian District (FTD) increases, but its proportion has a decreasing trend, and the proportion of the highest risk area within Longgang District (LGD) has an increasing trend. The risk zoning map can better reflect the risk distribution of the basin and provide a scientific basis for early warning of flood prevention and drainage in the Shenzhen River basin.

Background The associations between APOE genotype and early cognitive impairment and long-term functional prognosis after acute ischemic stroke (AIS) are uncertain. Objective To investigate the associations between APOE genotype and early cognitive impairment and long-term functional prognosis after AIS. Methods Our study was a single-center, prospective cohort study, that included 109 patients with AIS. At baseline, APOE genotype, cognition and white matter hyperintensities (WMH) were assessed within 2 weeks of stroke onset. At 3 months and 18 months, the modified Rankin scale (mRS) was used to assess the functional outcome after stroke. Results ε2 carriers had better cognitive performance than ε2 noncarriers did in the Montreal Cognitive Assessment (MoCA, p  = 0.003) and the Trail Making Test (TMT, p  = 0.038). Multivariate logistic regression analysis revealed that ε2 was an independent protective factor for early post-stroke cognitive impairment (OR 0.213, 95% CI 0.055–0.820), whereas ε4 was not associated with early post-stroke cognitive impairment (OR 2.582, 95% CI 0.314–21.219). ε2 had no significant effect on WMH, whereas ε4 aggravated WMH, especially in the deep white matter (DWM). No significant interaction effect between the Fazekas score and ε2 on early post-stroke cognitive impairment was found. Female sex (OR 7.081, 95% CI 2.531–19.813), admission NIHSS score (OR 1.265, 95% CI 1.062–1.507), and DWM Fazekas score (OR 2.224, 95% CI 1.106–4.469) were independent risk factors for long-term unfavorable prognosis after ischemic stroke. Conclusion ε2 was associated with reduced risk of early post-stroke cognitive impairment, but not with the favorable long-term functional prognosis after stroke.

Mining-induced earthquakes have been very frequent in recent years due to increasing mechanized mining. Compared with natural earthquakes, even a small one may cause significant damage to the mine area and its surroundings. Source type identification is important for better understanding the physical processes and is a crucial and fundamental issue for hazard assessment and emergency rescue in the mining environment. The moment tensor (MT) theory plays a pivotal role in distinguishing different source types. In this study, we concentrated on two strong reported “mine collapse earthquakes” in Qufu (M L 3.2, July 13, 2020) and Zoucheng (M L 2.9, June 09, 2020), Shandong Province, China. Seismograms from regional seismic stations were utilized to calculate the full moment tensors through low-frequency full-waveform inversion. Our results show that the two studied events exhibit notably different source types. The DC (Double-Couple) component of both events are 5% (Qufu) and 60% (Zoucheng), respectively. The Qufu event which contains approximately 75% closing crack component, is more consistent with the theoretical models of collapse seismic source. However, the Zoucheng event, which exhibits a significant proportion of DC components, demonstrates characteristics typical of shear failure. Focusing on the Zoucheng event, which occurred at the Dongtan Coal Mine, further research was conducted on a local mining scale. Analyzed in conjunction with microseismic sensor data, geologic setting, and mining progress, we illustrated that the source type of Zoucheng event is not a collapse one. The fracture slip of a thick-hard roof due to an overlying load, characterized by a large DC component, is a plausible geomechanical interpretation. Article Highlights Distinguishing between different source types is key to understanding their physical processes and evaluating hazard. We employed the method of regional moment tensor inversion to analyze the source types and mechanisms for the Qufu and the Zoucheng events. The Zoucheng event was further researched at a local mining scale, analyzing microseismic sensor data in conjunction with the geological setting and mining progress.

The gene kcnma1 encodes the α-subunit of high-conductance calcium- and voltage-dependent K + (BK) potassium channel. With the development of generation gene sequencing technology, many KCNMA1 mutants have been identified and are more closely related to generalized epilepsy and paroxysmal dyskinesia. Here, we performed a genetic screen of 26 patients with febrile seizures and identified a novel mutation of KCNMA1 (E155Q). Electrophysiological characterization of different KCNMA1 mutants in HEK 293T cells, the previously-reported R458T and E884K variants (not yet determined), as well as the newly-found E155Q variant, revealed that the current density amplitude of all the above variants was significantly smaller than that of the wild-type (WT) channel. All the above variants caused a positive shift of the I-V curve and played a role through the loss-of-function (LOF) mechanism. Moreover, the β4 subunit slowed down the activation of the E155Q mutant. Then, we used kcnma1 knockout (BK KO) mice as the overall animal model of LOF mutants. It was found that BK KO mice had spontaneous epilepsy, motor impairment, autophagic dysfunction, abnormal electroencephalogram (EEG) signals, as well as possible anxiety and cognitive impairment. In addition, we performed transcriptomic analysis on the hippocampus and cortex of BK KO and WT mice. We identified many differentially expressed genes (DEGs). Eight dysregulated genes [i.e., (Gfap and Grm3 associated with astrocyte activation) (Alpl and Nlrp10 associated with neuroinflammation) (Efna5 and Reln associated with epilepsy) (Cdkn1a and Nr4a1 associated with autophagy)] were validated by RT-PCR, which showed a high concordance with transcriptomic analysis. Calcium imaging results suggested that BK might regulate the autophagy pathway from TRPML1. In conclusion, our study indicated that newly-found point E155Q resulted in a novel loss-of-function variant and the dysregulation of gene expression, especially astrocyte activation, neuroinflammation and autophagy, might be the molecular mechanism of BK-LOF meditated epilepsy.

The quality of real-time waveform data from seismic networks not only directly affects the accuracy of seismic positioning accuracy, but also has an irreversible impact on the credibility of in-depth research findings in seismic disciplines. The article introduces an engineering perspective evaluation method for seismic data quality assessment, and uses real-time waveform data from the seismic station network in Shandong to form a visualization report on the quality of seismic quasi-real-time data, so as to determine the data quality of the seismic station network more intuitively and accurately.

Nonlinearities in lattices with topological band structures can induce topological interfaces in the bulk of structures and give rise to bulk solitons in the topological bandgaps. Here we study a photonic Chern insulator with saturable nonlinearity and show the existence of topological bulk solitons. The fundamental bulk solitons exhibit as semi-vortex solitons, where only one pseudospin component has a nonzero vorticity. The bulk solitons have equal angular momentum at different valleys. This phenomenon is a direct outcome of the topology of the linear host lattice and the angular momentum can be changed by switching the sign of the nonlinearity. The bulk solitons bifurcate from the linear bulk band edge and terminate when their powers saturate. We find that these bulk solitons are stable within the whole spectrum range. Moreover, these bulk solitons are robust against lattice disorders both from on-site energies and hopping amplitudes. Our work extends the study of Chern insulators into the nonlinear regime and highlights the interplay between topology and nonlinearity. The combination of nonlinearity and topology has recently attracted significant attention in the field of optical physics. This work considers a photonic Chern insulator in the nonlinear regime and explores the properties of topological bulk solitons holding the stability and robustness, which contributes to the field of nonlinear topological photonics and provides further physical understandings towards other photonic topological insulators with nonlinearity.

This phenomenological study explored the experience of participation in square sports in China and the social mechanisms by which they can be sustained. Ten study participants were selected through a purposeful sampling method. The findings indicate that their physical and mental health were either maintained or improved as they engaged in square sports. They also experienced reduced feelings of loneliness and an increase in their sense of belonging through exchanges with other members of their teams. They enjoyed the freedom from cost and spatial restrictions in pursuing leisure activities. However, conflicts also arose with other groups, mainly related to securing space in the squares. Additionally, the study found that conflicts between participants and non-participants in square sports emerged as a social problem. The social mechanisms by which square sports can be sustained were identified as people-led voluntary participation, pride in square sports, and the reproduction of economic capital using human resources.

[This corrects the article DOI: 10.3389/fnins.2019.01393.].