Inhibitory role of TRIP-Br1 oncoprotein in anticancer drug-mediated programmed cell death via mitophagy activation

Chemotherapy has been widely used as a clinical treatment for cancer over the years. However, its effectiveness is limited because of resistance of cancer cells to programmed cell death (PCD) after treatment with anticancer drugs. To elucidate the resistance mechanism, we initially focused on cancer cell-specific mitophagy, an autophagic degradation of damaged mitochondria. This is because mitophagy has been reported to provide cancer cells with high resistance to anticancer drugs. Our data showed that TRIP-Br1 oncoprotein level was greatly increased in the mitochondria of breast cancer cells after treatment with various anticancer drugs including staurosporine (STS), the main focus of this study. STS treatment increased cellular ROS generation in cancer cells, which triggered mitochondrial translocation of TRIP-Br1 from the cytosol via dephosphorylation of TRIP-Br1 by protein phosphatase 2A (PP2A). Up-regulated mitochondrial TRIP-Br1 suppressed cellular ROS levels. In addition, TRIP-Br1 rapidly removed STS-mediated damaged mitochondria by activating mitophagy. It eventually suppressed STS-mediated PCD via degradation of VDACI, TOMM20, and TIMM23 mitochondrial membrane proteins. TRIP-Br1 enhanced mitophagy by increasing expression levels of two crucial lysosomal proteases, cathepsins B and D. In conclusion, TRIP-Br1 can suppress the sensitivity of breast cancer cells to anticancer drugs by activating autophagy/mitophagy, eventually promoting cancer cell survival.     

化感物质对枯草芽孢杆菌(Bacillus subtilis)在厌氧条件下的生长及反硝化作用的影响

研究由秸秆腐解产生的化感物质 :阿魏酸 ( t-FA)、对羟基苯甲酸 ( p-HA)和苯甲酸 ( BA)在不同浓度下对厌氧培养的枯草芽孢杆菌 ( Bacillussubtilis)的生长及其反硝化活性的影响。结果表明 ,3种浓度的阿魏酸 ( 5.1 5、2 .58、0 .2 6mmol/L)均表现出对枯草芽孢杆菌的生长有抑制作用。对羟基苯甲酸 ( 0 .3 6、3 .62、7.2 4 mmol/L )对生长影响不明显。 8.1 9mmol/L和 4 .0 9mmol/L的苯甲酸有一定的刺激作用 ,而 0 .4 1 mmol/L的苯甲酸与对照无差别。实验表明枯草芽孢秆菌不仅能转化 NO- 3生成 NO- 2 ,而且还能转化 NO- 2 生成 N2 O。 3种化感物质对 NO- 3的转化均表现抑制作用 ,其抑制作用强弱依次为阿魏酸 >对羟基苯甲酸 >苯甲酸。高浓度的抑制作用强于低浓度。阿魏酸在 5.1 5mmol/L和 2 .58mmol/L浓度下 ,其抑制作用的差异显著性分别为 P<0 .0 1 ,P<0 .0 5。 NO- 2 的生成与 NO- 3的减少相互有关联 ,第 3天测定时 ,各处理中NO- 3急剧减少 ,而 NO- 2 急剧增加。在阿魏酸、苯甲酸处理中的 NO- 2 积累高峰在第 3天、第 4天 ,然后下降。而在对羟基苯甲酸的处理中 NO- 2 的积累一直上升 ,在第 6天的观察中仍未出现下降趋势。 3种化感物质均能抑制 N2 O的生成 ,至于在田间的抑制效果尚需进一步试验     

Depression compromises antiviral innate immunity via the AVP-AHI1-Tyk2 axis

Depression is a serious public-health issue. Recent reports have suggested higher susceptibility to viral infections in depressive patients. However, how depression affects antiviral innate immune signaling remains unknown. Here, we revealed a reduction in expression of Abelson helper integration site 1 (AHI1) in the peripheral blood mononuclear cells (PBMCs) and macrophages from the patients with major depressive disorder (MDD), which leads to attenuated antiviral immune response. We found that depression-related arginine vasopressin (AVP) induces reduction of AHI1 in macrophages. Further studies demonstrated that AHI1 is a critical stabilizer of basal type-I-interferon (IFN-I) signaling. Mechanistically, AHI1 recruits OTUD1 to deubiquitinate and stabilize Tyk2, while AHI1 reduction downregulates Tyk2 and IFN-I signaling activity in macrophages from both MDD patients and depression model mice. Interestingly, we identified a clinical analgesic meptazinol that effectively stimulates AHI1 expression, thus enhancing IFN-I antiviral defense in depression model mice. Our study promotes the understanding of the signaling mechanisms of depression-mediated antiviral immune dysfunction, and reveals meptazinol as an enhancer of antiviral innate immunity in depressive patients.Subject terms: Innate immunity, Ubiquitylation, Cell signalling     

SWAT模型对景观格局变化的敏感性分析——以丹江口库区老灌河流域为例

景观的空间配置与类型组成能够对流域的产流、产沙及非点源污染产生影响。在以往SWAT模型研究中,往往默认水文模型考虑了该影响。为分析SWAT模型对不同景观格局变化的敏感性,根据老灌河流域2000年土地利用在各子流域的组成,模拟研究区更为破碎、复杂的景观空间配置,通过设置多套试验参数,利用SWAT模型生成基于不同景观格局的模拟结果。结果表明,SWAT模型不能反映除坡度和面积变化之外的景观水平下各斑块之间因景观空间格局改变对流域产流、产沙以及非点源污染的影响;模型通过其他参数的调整,弥补了模型分析数据的不足,使实测数据与模型部分结果高度吻合。这表明,一个能够反映流域部分水文特征的SWAT模型,未必是对研究区真实情形的模拟,而是各个参数间平衡的结果。因此,在利用SWAT模型分析模拟景观变化时,不应默认模型能够模拟景观空间格局改变对流域水文过程的影响,同时研究者可以通过划分坡度带,提高模型对不同坡度土地利用的敏感性。     

产β-1,3-葡聚糖酶植物内生放线菌的筛选及抑菌活性研究

本研究采用透明圈法, 对217株植物内生放线菌产β-1,3-葡聚糖酶进行了检测, 结果表明: 45.6%的菌株能够产生β-1,3-葡聚糖酶, 黄瓜内生放线菌中的产酶菌株最多为38个; 不同植物来源的内生放线菌中具有产β-1,3-葡聚糖酶能力的菌株比例不同, 其中黄精中的产酶菌株比例最高, 达到88.9%。产酶菌株粗酶液对油菜菌核病菌的抑菌活性测定结果发现, 36个产酶菌株的粗酶液表现出不同程度的抑制作用, 占总产酶菌株的36.4%, 其中菌株gCLA4的粗酶液能够完全抑制病菌菌丝生长。对gCLA4菌株产酶     

Exercise increases the release of NAMPT in extracellular vesicles and alters NAD + activity in recipient cells

Aging is associated with a loss of metabolic homeostasis, with cofactors such as nicotinamide adenine dinucleotide (NAD⁺) declining over time. The decrease in NAD⁺ production has been linked to the age‐related loss of circulating extracellular nicotinamide phosphoribosyltransferase (eNAMPT), the rate‐limiting enzyme in the NAD⁺ biosynthetic pathway. eNAMPT is found almost exclusively in extracellular vesicles (EVs), providing a mechanism for the distribution of the enzyme in different tissues. Currently, the physiological cause for the release of eNAMPT is unknown, and how it may be affected by age and physical exercise. Here, we show that release of small EVs into the bloodstream is stimulated following moderate intensity exercise in humans. Exercise also increased the eNAMPT content in EVs, most prominently in young individuals with higher aerobic fitness. Both mature fit and young unfit individuals exhibited a limited increase in EV‐eNAMPT release following exercise, indicating that this mechanism is related to both the age and physical fitness of a person. Notably, unfit mature individuals were unable to increase the release of eNAMPT in EVs after exercise, suggesting that lower fitness levels and aging attenuate this important signalling mechanism in the body. EVs isolated from exercising humans containing eNAMPT were able to alter the abundance of NAD⁺ and SIRT1 activity in recipient cells compared to pre‐exercise EVs, indicating a pathway for inter‐tissue signalling promoted through exercise. Our results suggest a mechanism to limit age‐related NAD⁺ decline, through the systemic delivery of eNAMPT via EVs released during exercise.     

Development of a Peristaltic Micropump for Bio-Medical Applications Based on Mini LIPCA

This paper presents the design, fabrication, and experimental characterization of a peristaltic micropump. The micropump is composed of two layers fabricated from Polydimethylsiloxane （PDMS） material. The first layer has a rectangular channel and two valve seals. Three rectangular mini lightweight piezo-composite actuators are integrated in the second layer, and used as actuation parts. Two layers are bonded, and covered by two Polymethyl Methacrylate （PMMA） plates, which help increase the stiffness of the micropump. A maximum flow rate of 900μL.min 1 and a maximum backpressure of 1.8 kPa are recorded when water is used as pump liquid. We measured the power consumption of the micropump. The micropump is found to be a promising candidate for bio-medical application due to its bio-compatibility, portability, bidirectionality, and simple effective design.     

基因型多样性对羊草种群年龄结构的影响

基因型多样性作为遗传多样性的重要组成部分,不仅在群落水平,而且在种群水平均可以发挥重要生态作用。以羊草（Leymus chinensis）为研究对象,设置5种基因型多样性梯度试验控制小区,进行基因型多样性对羊草种群年龄结构的影响研究。结果表明：随基因型多样性梯度的逐步增加,2a分蘖株生物量和数量均显著增加（P<0.05）;1-4龄级羊草根茎生物量、长度和干物质积累量多数呈极显著性增加的变化趋势（P<0.01）。在1、2、4、8和12种基因型多样性梯度时,分蘖株生物量及数量年龄结构均以1a或2a分蘖株所占比例为最高,年龄结构表现为增长型或稳定型;而羊草种群根茎生物量和长度也以2a根茎所占比例为最高,年龄结构表现为稳定型。随基因型多样性水平的增加,羊草种群分蘖株数量和生物量的年龄结构从增长型向稳定型过渡,但根茎长度和生物量的年龄结构均为稳定型。12基因型多样性水平的4龄级分蘖株和根茎的特征高于其他基因型多样性水平。因此,在不同基因型多样性水平羊草种群分蘖株和根茎具有增长型或稳定型的年龄结构,适当的基因型多样性数量显著促进了各龄级羊草分蘖株和根茎的生物量和数量特征的升高,但高度的基因型多样性水平会增加羊草种群中高龄级的分蘖株和根茎所占的比例,种群发展表现出衰退信号。     

格网尺度下典型旅游城市生态服务价值估算和时空分异特征——以三亚为例

以典型旅游城市三亚市为案例地,利用2006-2018年4期Landsat遥感影像数据,借助ENVI、ArcGIS平台定量识别土地利用演变特征,在1km×1km格网尺度下估算旅游地生态系统服务价值,并结合空间探索性数据分析揭示生态系统服务价值时空分异特征及其与旅游地发展的时空耦合关系。结果表明：（1）2006-2018年间,三亚市生态系统服务价值总量呈逐年下降趋势,由6.73×10⁹元降至5.76×10⁹元,累计减少9.78×10⁸元;（2）空间格局上,三亚市呈"南低北高"空间分异格局,2006-2018年增值区域连片分布于崖州区、天涯区、吉阳区南部区域,且呈逐年减少趋势,减值区域集聚于天涯区东北部、海棠区;（3）空间集聚上,生态系统服务价值截面各年份均呈显著空间正相关且相关性先降后增。高高集聚区位于天涯区北部区域,低低集聚区分布于沿海、海湾地区;（4）旅游发展与生态系统服务价值时空演化特征关联性较强。三亚市天涯区北部林地生态环境良好,生态系统服务价值略有下降但绝对数值稳定,是生态系统服务价值主要来源;旅游发展较为迅速的三亚湾、崖州湾以及海棠湾,相对增值区域较多,但绝对生态系统服务价值损失显著,严重滞后于其他区域。