Downregulation of PPARα mediates FABP1 expression,contributing to IgA nephropathy by stimulating ferroptosis in human mesangial cells

Immunoglobulin A nephropathy (IgAN) is the commonest primary glomerulonephritis, and a major cause of end-stage renal disease; however, its pathogenesis requires elucidation. Here, a hub gene, FABP1, and signaling pathway, PPARα, were selected as key in IgAN pathogenesis by combined weighted gene correlation network analysis of clinical traits and identification of differentially expressed genes from three datasets. FABP1 and PPARα levels were lower in IgAN than control kidney, and linearly positively correlated with one another, while FABP1 levels were negatively correlated with urinary albumin-to-creatinine ratio, and GPX4 levels were significantly decreased in IgAN. In human mesangial cells (HMCs), PPARα and FABP1 levels were significantly decreased after Gd-IgA1 stimulation and mitochondria appeared structurally damaged, while reactive oxygen species (ROS) and malondialdehyde (MDA) were significantly increased, and glutathione and GPX4 decreased, relative to controls. GPX4 levels were decreased, and those of ACSL4 increased on siPPARα and siFABP1 siRNA treatment. In PPARα lentivirus-transfected HMCs stimulated by Gd-IgA1, ROS, MDA, and ACSL4 were decreased; glutathione and GPX4, and immunofluorescence colocalization of PPARα and GPX4, increased; and damaged mitochondria reduced. Hence, PPARα pathway downregulation can reduce FABP1 expression, affecting GPX4 and ACSL4 levels, causing HMC ferroptosis, and contributing to IgAN pathogenesis.     

One night of sleep deprivation induces release of small extracellular vesicles into circulation and promotes platelet activation by small EVs

Extracellular vesicles (EVs) are emerging as key players in intercellular communication. Few studies have focused on EV levels in subjects with sleep disorders. Here, we aimed to explore the role of acute sleep deprivation on the quantity and functionality of circulating EVs, and their tissue distribution. EVs were isolated by ultracentrifugation from the plasma of volunteers and animals undergoing one night of sleep deprivation. Arterio‐venous shunt, FeCl₃ thrombus test and thrombin‐induced platelet aggregation assay were conducted to evaluate the in vivo and in vitro bioactivity of small EVs. Western blotting was performed to measure the expression of EV proteins. The fate and distribution of circulating small EVs were determined by intravital imaging. We found that one night of sleep deprivation triggers release of small EVs into the circulation in both healthy individuals and animals. Injection of sleep deprivation‐liberated small EVs into animals increased thrombus formation and weight in thrombosis models. Also, sleep deprivation‐liberated small EVs promoted platelet aggregation induced by thrombin. Mechanistically, sleep deprivation increased the levels of HMGB1 protein in small EVs, which play important roles in platelet activation. Furthermore, we found sleep deprivation‐liberated small EVs are more readily localize in the liver. These data suggested that one night of sleep deprivation is a stress for small EV release, and small EVs released here may increase the risk of thrombosis. Further, small EVs may be implicated in long distance signalling during sleep deprivation‐mediated adaptation processes.     

宁夏东部荒漠草原灌丛引入对土壤水分动态及亏缺的影响

全球气候变化背景下,荒漠草原人工灌丛引入加速其灌丛化进程,对草原土壤水分产生重要影响。为了解宁夏东部荒漠草原灌丛引入过程中土壤水分动态及亏缺现状,选取了封育草地、放牧草地、不同年限(3a、12a、22a)和间距(40 m、6 m、2 m)灌丛柠条(Caragana korshinskii)地进行土壤水分测定,并利用土壤水分相对亏缺指数(compared soil water deficit index,CSWDI)、样地土壤水分相对亏缺指数(plot compared soil water deficit index,PCSWDI)对土壤水分亏缺进行定量分析。结果表明:灌丛引入过程中不同年限、间距灌丛地0—200 cm土层土壤含水量均显著低于封育草地与放牧地(P<0.05);各样地季节动态均表现为春季返潮、夏季消耗、秋季蓄积的季节规律,但不同年限、间距灌丛地表现为春季返潮微弱,土壤含水量仅为7.80%—10.90%,显著低于封育草地和放牧地(11.90%—16.09%);灌丛引入过程中各灌丛地0—100 cm有效储水量(-16.98—18.69 mm)均低于封育草地(34.67 ...     

强化类球红细菌辅因子NADPH再生以提高法尼醇的产量

法尼醇(Farnesol,FOH)是由焦磷酸异戊烯基(IPP)和焦磷酸二甲基烯丙基(DMAPP)合成的法尼酰基焦磷酸盐(FPP)去焦磷酸化作用生成的。在类球红细菌中IPP和DMAPP是由MEP途径生成,而完整的MEP途径需要消耗大量的辅因子NADPH,增加胞内NADPH的量有可能强化FOH的合成。文中从增加NADPH的生成和降低NADPH的消耗这两个策略出发,分别干扰了编码6-磷酸葡萄糖异构酶基因(pgi)和谷氨酸脱氢酶基因(gdhA)的表达,同时强化了磷酸戊糖途径中6-葡萄糖磷酸脱氢酶基因(zwf)和6-葡萄糖酸磷酸脱氢酶基因(gnd)的表达。实验结果表明,经改造的菌株NADPH含量显著增加,干扰菌株中菌株RSpgii的产量较高,为3.91 mg/g,在过表达的菌株中同时过表达zwf和gnd基因的重组菌株(RSzg)的FOH产量提高到了3.43 mg/g。为了获得FOH产量更高的菌株,以RSpgii为出发菌株,分别与zwf和gnd组合调控,获得的菌株RSzgpi的产量达到了最高量为4.48 mg/g,是出发菌株RS-GY2产率的2.24倍。     

温度诱导Targetron系统用于大肠杆菌高效基因失活

构建基于Te I3c/4c嗜热二型内含子的温度诱导Targetron基因失活系统(Thermotargetron),并应用于中温微生物基因编辑。在大肠杆菌HMS174(DE3)基因组中,选择Subunitofflagellum基因(fliC)和C4dicarboxylate orotate:H+symporter基因(dctA)为靶基因。根据Te I3c/4c DNA识别规则,在fliC和dctA基因中选择fliC489a、fliC828s、fliC1038s和dctA2a位点为基因打靶位点。使用重叠延伸PCR方法,基于pHK-TT1A质粒构建打靶载体。打靶载体转化HMS174菌株,对数期转化子培养液48℃热激1h后涂布于氯霉素抗性LB平板上。使用菌落PCR和DNA测序检测突变株并计算基因失活效率。获得突变株后,通过琼脂穿刺和碳源代谢实验,鉴定ΔfliC、ΔdctA突变株表型变化。菌落PCR测序结果表明,Te I3c/4c插入到fliC和dctA基因设计位点,且打靶效率高达100%。突变株表型验证实验表明,ΔfliC突变株运动能力显著下降,ΔdctA突变株苹果酸代谢能力缺失。综上所述,...     

樟树叶片挥发性有机物释放季节动态和日动态变化规律

采用动态顶空采集法和热脱附-气质联用技术,对不同季节和一天内不同时间点樟树叶片释放的挥发性有机物(VOCs)成分含量及其变化规律进行了分析。结果表明:全年樟树叶片释放的VOCs共计78种,其中萜烯类(19种)和烷烃类(18种)化合物种类较多; 32种樟树叶片释放的挥发性成分相对含量在不同季节存在显著差异(P<0.05); 3月份释放的VOCs种类最为丰富,萜烯类化合物相对含量最高(43.49%),主要为1-石竹烯、D-柠檬烯和α-蒎烯,其他月份释放的VOCs则以烷烃类和醇类为主;春季,樟树叶片在绝大多数时间点释放VOCs以萜烯类化合物为主,且早上8:00释放的萜烯类化合物相对含量最大。综上结果认为,樟树是营造保健型生态园林的理想树种,其叶片释放的VOCs中富含多种对人体健康有益的萜烯类化合物,春季的早晨是进行森林康养活动的最佳时间。     

若尔盖人-狼冲突现状与管理研究

大中型食肉动物肇事事件导致人类与野生动物关系恶化,给生物多样性保护工作带来巨大的挑战。若尔盖湿地是我国三大湿地之一,湿地、草原分布广泛,生物多样性丰富,畜牧业发达,但近年来狼(Canis lupus)捕杀牲畜的肇事事件时有发生。为了解若尔盖野生狼肇事件的空间分布以及牧民对人-狼冲突管理的看法,本研究于2022年对若尔盖县13个乡镇83个行政村进行走访调查。结果表明：(1)多数受访者(66.0%)认为在过去5年内,若尔盖县野生狼数量有所增加;(2)狼肇事事件具有明显的空间分异性,最严重的是包座乡。包座乡临近山区,该区域牧场面积广阔、牧民饲养牲畜数量多等原因导致该镇发生狼肇事事件较多;(3)对于狼肇事,绝大多数牧民(85.0%)更希望采取经济补偿或者驱赶措施,只有少数牧民(9.4%)希望采取捕杀的措施;(4)影响牧民对狼肇事管理措施的偏好因子中,受教育程度、年龄、民族以及被杀牲畜数量有显著影响。建议加强狼种群监测管理,采取措施减少狼捕杀牲畜,优化补偿机制,缓解当地牧民与狼之间的矛盾。本研究为当前若尔盖县野生动物保护和管理决策提供了依据,对其他地区大型食肉动物与当地居民冲突管理具有借鉴意义。