Attenuation of kainic acid-induced epilepsy by butyrate is associated with inhibition of glial activation

Purpose: To investigate the function and potential therapeutic relevance of butyrate in epilepsy using rat models of kainic acid (KA)-induced epilepsy.Methods: The neurotoxin KA was applied to rats and rat astrocytes to establish models of epilepsy in vivo and in vitro. Multiple parameters, including behavioural seizure scores, were evaluated in rats and rat astrocytes treated with KA alone or in combination with butyrate. Western blot was performed to examine the levels of phosphorylated extracellular signal-related kinase (p-ERK), proinflammatory cytokine (IL-1ß), and glial fibrillary acidic protein (GFAP).Results: Significant increases were observed in the seizure-related proteins p-ERK and GFAP and in the proinflammatory cytokine IL-1ß in KA-treated rats and rat astrocytes (p < 0.05). Butyrate treatment attenuated KA-induced epileptic behaviour in rats and significantly reduced the expression of p-ERK, GFAP, and IL-1ß in a dose-dependent manner (p < 0.05).Conclusion: Butyrate has potential as a treatment for epilepsy by inhibiting the activation of p-ERK, astrogliosis, and inflammation, which were induced by KA in rats and rat astrocytes.Keywords: Kainic acid, Epilepsy, Butyrate, Glial activation, Astrogliosi

Enhanced betatron radiation by steering a laser-driven plasma wakefield with a tilted shock front

We have experimentally realized a scheme to enhance betatron radiation by manipulating transverse oscillation of electrons in a laser-driven plasma wakefield with a tilted shock front (TSF). Very brilliant betatron x-rays have been produced with significant enhancement both in photon yield and peak energy but almost maintain the e-beam energy spread and charge. Particle-in-cell simulations indicate that the accelerated electron beam (e beam) can acquire a very large transverse oscillation amplitude with an increase in more than 10-fold, after being steered into the deflected wakefield due to the refraction of the driving laser at the TSF. Spectral broadening of betatron radiation can be suppressed owing to the small variation in the peak energy of the low-energy-spread e beam in a plasma wiggler regime. It is demonstrated that the e-beam generation, refracting, and wiggling can act as a whole to realize the concurrence of monoenergetic e beams and bright x-rays in a compact laser-wakefield accelerator

Menin Deficiency Leads to Depressive-like Behaviors in Mice by Modulating Astrocyte-Mediated Neuroinflammation

厦门大学医学院、神经科学研究所张杰教授团队发现了抑郁症新的致病基因MEN1，并阐明了MEN1调控星形胶质细胞炎症导致抑郁发生发展的新机制，为抑郁症的诊治提供了新靶点和方向。抑郁症是严重威胁人类健康的重大神经系统疾病，危及全球30%的人口。但对其发病机制并不清楚。张杰教授团队发现，在慢性不可预测以及LPS处理的模拟抑郁小鼠模型中，多发性内分泌肿瘤蛋白(menin)在大脑中的表达显著降低，并且在星形胶质细胞中降低最明显。为了研究menin是否参与了小鼠抑郁表型的产生，研究团队制作了多种神经系统menin条件性敲除小鼠。通过对这些小鼠行为学的检测，锁定了只有在星形胶质细胞中敲除menin后，小鼠才会表现出抑郁样表型。证实了menin可能是通过调控星形胶质细胞的功能促进了抑郁的发生。 MEN1基因的突变会导致多发性内分泌肿瘤，而内分泌的紊乱和抑郁等精神疾病有着密切的联系。下丘脑-垂体-肾上腺轴（HPA轴）的功能紊乱直接参与了抑郁的产生。基于此研究团队推测MEN1的基因突变是否也会导致抑郁的发生。通过和中国医学科学院基础所的许琪教授合作，研究团队对1000多例重度抑郁患者和800多例对照人群进行了MEN1基因的外显子测序。通过测序发现MEN1的一个SNP s375804228和抑郁的发生有着显著关联。该SNP导致menin第503位的氨基酸由G突变成D。通过功能研究进一步证实该突变可以阻断menin和p65的结合，从而过度激活NF-κB-IL-1β通路，导致神经炎症的发生。 张杰，厦门大学特聘教授、博士生导师。国家优秀青年科学基金；教育部新世纪优秀人才；福建省杰出青年科学基金；厦门市五四青年奖章等获得者。2011年8月加入厦门大学医学院神经科学研究所担任教授至今。张杰博士主要从事重大神经系统疾病（老年痴呆、帕金森、抑郁症、自闭症、术后认知障碍、胶质瘤）等的发病机制和药物开发研究。至今以第一作者或者通讯作者在国际知名期刊发表研究论文21篇。其中回国独立开展研究工作以后，作为通讯作者在 Neuron，Cell Reports, PNAS, The Journal of Neuroscience, Clinical Cancer Research，Cell Death and Disease, JBC, Chemistry，Chem. Biol. Drug Des.等杂志上发表多篇研究论文。【Abstract】Astrocyte dysfunction and inflammation are associated with the pathogenesis of major depressive disorder (MDD). However, the mechanisms underlying these effects remain largely unknown. Here, we found that multiple endocrine neoplasia type 1 (Men1; protein: menin) expression is attenuated in the brain of mice exposed to CUMS (chronic unpredictable mild stress) or lipopolysaccharide. Astrocyte-specific reduction of Men1 (GcKO) led to depressive-like behaviors in mice. We observed enhanced NF-κB activation and IL-1β production with menin deficiency in astrocytes, where depressive-like behaviors in GcKO mice were restored by NF-κB inhibitor or IL-1β receptor antagonist. Importantly, we identified a SNP, rs375804228, in human MEN1, where G503D substitution is associated with a higher risk of MDD onset. G503D substitution abolished menin-p65 interactions, thereby enhancing NF-κB activation and IL-1β production. Our results reveal a distinct astroglial role for menin in regulating neuroinflammation in depression, indicating that menin may be an attractive therapeutic target in MDD.We thank Prof. Guanghui Jin (Xiamen University) and Prof. Xianxin Hua (University of Pennsylvania) for providing the Men1-floxp mice. This work was supported by the National Natural Science Foundation of China (grants 81522016, 81271421, and 31571055 to J.Z.; 81625008 and 31430048 to Q.X.; 81630026 to Z.Y.; 81771163 and U1405222 to H.X.; U1505227 to G.B.; 81472725 to W.M.), the Natural Science Foundation of Fujian Province of China (grant 2013J01147 and 2014J06019 to J.Z.), the Fundamental Research Funds for the Central Universities (grants 20720150062 and 20720180049 to J.Z.), the National Key Research and Development Program of China (2016YFC1305903), and CAMS Innovation Fund for Medical Sciences (grant 2016I2M1004 to Q.X.).研究工作得到国家自然科学基金项目（81522016、81271421、31571055）以及厦门大学校长基金等资助

Comparative Analyses of Grain Quality in Response to High Temperature during the Grain-Filling Stage between <i>Wx</i>^a and <i>Wx</i>^b under <i>Indica</i> and <i>Japonica</i> Backgrounds

Amylose content controlled by Wx determines rice grain quality, which is easily affected by high temperature. Wxa and Wxb are the two typical Wx alleles in rice, however, their effects on quality formation in response to high temperature under the backgrounds of indica rice and japonica rice have not been systematically compared. In this study, the near-isogenic lines (NILs) of Wxa and Wxb with japonica rice 2661 and indica rice 3611 backgrounds were treated by high temperature during the grain-filling stages. High temperature accelerated the grain ripening process, decreased the thousand-kernel weight, and increased the chalkiness degree of all rice samples. However, these traits of Wx NILs with 3611 background were more susceptible to high temperature than those with 2661 background. Furthermore, high-temperature treatment decreased the amylose contents (AC) and starch viscosities but increased the gelatinization temperature of all the Wx NILs. The 3611-Wxa was atypical Wxa-type rice, whose AC was more sensitive to high temperature. The AC result was consistent with quantitative analysis of GBSSI by Western blot. In addition, the effects of Wx genotype and genetic background on rice physicochemical quality (such as the gel consistencies, starch crystallinity, and the morphological structure of starch grains) in response to high temperature were systematically analyzed. These results have important guiding significance for rice-quality improvement under high-temperature climate

Nonanatomical Reduction of Femoral Neck Fractures in Young Patients (≤65 Years Old) with Internal Fixation Using Three Parallel Cannulated Screws

Purpose. The study is aimed at investigating the association between different reduction classifications (anatomic reduction, positive buttress position reduction, and negative buttress position reduction) and two end points (complications and reoperations). Methods. The study retrospectively analyzed 110 patients undergoing internal fixation with three parallel cannulated screws from January 2012 to January 2019 in Huashan Hospital. Based on the principles of the “Gotfried reduction,” all enrolled patients were divided into three groups: anatomic reduction, positive buttress position reduction, and negative buttress position reduction intraoperatively or immediately after surgery. Clinical characteristics including age, sex, side, Garden classification, Pauwels classification, fracture level, reduction classification, Garden alignment index angles, cortical thickness index (CTI), tip-caput distance (TCD), angle of the inferior screw, and the two ending points (complications and reoperations) were included in the statistical analysis. The Mann-Whitney U-test, the chi-square test, Fisher’s exact test, and multiple logistic regression analysis were used in the study. Results. Of the 110 patients included in our study, the mean±standard deviation SD of age was 51.4±10.4 years; 41 patients showed anatomic reduction, 35 patients showed positive buttress position reduction, and 34 patients showed negative buttress position reduction. For the outcomes, 24 patients (anatomic reduction: 6 [14.6%]; positive buttress position reduction: 5 [14.3%]; negative buttress position reduction: 13 [38.2%]) had complications, while 18 patients (anatomic reduction: 5 [12.2%]; positive buttress position reduction: 3 [8.6%]; negative buttress position reduction: 10 [29.4%]) underwent reoperations after surgery. In the multivariate logistic regression analysis of complications, negative buttress position reduction (negative buttress position reduction vs. anatomic reduction, OR=4.309, 95%CI=1.137 to 16.322, and p=0.032) was found to be correlated with higher risk of complications. The same variable (negative buttress position reduction vs. anatomic reduction, OR=5.744, 95%CI=1.177 to 28.042, and p=0.031) was also identified as risk factor in the multivariate logistic regression analysis of reoperations. However, no significant difference between positive reduction and anatomical reduction was investigated in the analysis of risk factors for complications, not reoperations. Conclusion. Positive buttress position reduction of femoral neck fractures in young patients showed a similar incidence of complications and reoperations compared with those of anatomic reduction. For irreversible femoral neck fractures, if positive buttress position reduction has been achieved intraoperatively, it is not necessary to pursue anatomical reduction; however, negative reduction needs to be avoided