Pericyte-derived extracellular vesicle-mimetic nanovesicles ameliorate erectile dysfunction via lipocalin 2 in diabetic mice

Diabetes mellitus is one of the main causes of erectile dysfunction (ED). Men with diabetic ED do not respond well to oral phosphodiesterase-5 inhibitors owing to neurovascular dysfunction. Pericyte-derived extracellular vesicle-mimetic nanovesicles (PC-NVs) are known to promote nerve regeneration in a mouse model of cavernous nerve injury. Here, we report that administration of PC-NVs effectively promoted penile angiogenesis and neural regeneration under diabetic conditions, thereby improving erectile function. Specifically, PC-NVs induced endothelial proliferation and migration and reduced cell apoptosis under diabetic conditions. In addition, PC-NVs induced neural regeneration in STZ-induced diabetic mice in dorsal root ganglion and major pelvic ganglion explants in vivo and ex vivo under high-glucose conditions. We found that lipocalin 2 (Lcn2) is a new target of PC-NVs in this process, demonstrating that PC-NVs exert their angiogenic and nerve-regeneration effects by activating MAP kinase and PI3K/Akt and suppressing P53 signaling pathway in an Lcn2-dependent manner. Our findings provide new conclusive evidence that PC-NVs can promote neurovascular regeneration and recovery of erectile function under diabetic conditions via an Lcn2-dependent mechanism. Thus, local administration of PC-NVs may be a promising treatment strategy for the treatment of diabetic ED.     

渤海浮游动物群落生态特点Ⅰ.种类组成与群落结构

以１９５９年全国海洋普查浮游动物中网周年标本为材料,对渤海浮游动物的群落结构进行分析。渤海浮游动物群落以近岸广温种为主,主要优势种包括小拟哲水蚤（Ｐａｒａｃａｌａｎｕｓ ｐａｒｖｕｓ）、双毛纺锤水蚤（Ａｃａｒｔｉａ ｂｉｆｉｌｏｓａ）、强额拟哲水蚤（Ｐａｒａｃａｌａｎｕｓ ｃｒａｓｓｉｒｏｓｔｒｉｓ）、拟长腹剑水蚤（Ｏｉｔｈｏｎａ ｓｉｍｉｌｉｓ）、墨氏胸刺水蚤（Ｃｅｎｔｒｏｐａｇｅｓ ｍｃｍｕｒ     

A secreted ribonuclease effector from Verticillium dahliae localizes in the plant nucleus to modulate host immunity

The arms race between fungal pathogens and plant hosts involves recognition of fungal effectors to induce host immunity. Although various fungal effectors have been identified, the effector functions of ribonucleases are largely unknown. Herein, we identified a ribonuclease secreted by Verticillium dahliae (VdRTX1) that translocates into the plant nucleus to modulate immunity. The activity of VdRTX1 causes hypersensitive response (HR)‐related cell death in Nicotiana benthamiana and cotton. VdRTX1 possesses a signal peptide but is unlikely to be an apoplastic effector because its nuclear localization in the plant is necessary for cell death induction. Knockout of VdRTX1 significantly enhanced V. dahliae virulence on tobacco while V. dahliae employs the known suppressor VdCBM1 to escape the immunity induced by VdRTX1. VdRTX1 homologs are widely distributed in fungi but transient expression of 24 homologs from other fungi did not yield cell death induction, suggesting that this function is specific to the VdRTX1 in V. dahliae. Expression of site‐directed mutants of VdRTX1 in N. benthamiana leaves revealed conserved ligand‐binding sites that are important for VdRTX1 function in inducing cell death. Thus, VdRTX1 functions as a unique HR‐inducing effector in V. dahliae that contributes to the activation of plant immunity.     

广东阳春现代樟树树轮宽度变化及其对气候因子的响应

树木年轮方法定年准确、连续性强、分辨率高和易于获取复本等 ,成为全球气候变化研究的重要手段之一。在热带、亚热带地区 ,受树木生理特性的影响 ,树轮研究工作开展较少。通过广东阳春过渡热带现代樟树树木年轮宽度的变化 ,发现秋季降水是影响研究区樟树生长的重要因子。树轮记录的准 4～ 4 .92 a周期的树轮指数变化可能与厄尔尼诺的周期有关 ,即厄尔尼诺引起气候变化对树木生长产生影响。尽管樟树生长快 ,树轮不清晰 ,交叉定年困难 ,但由于研究区存在明显的旱季 ,樟树树轮仍然能够在一定程度上反映气候条件的影响。     

Direct adenylation from 5′-OH-terminated oligonucleotides by a fusion enzyme containing Pfu RNA ligase and T4 polynucleotide kinase

5′-Adenylated oligonucleotides (AppOligos) are widely used for single-stranded DNA/RNA ligation in next-generation sequencing (NGS) applications such as microRNA (miRNA) profiling. The ligation between an AppOligo adapter and target molecules (such as miRNA) no longer requires ATP, thereby minimizing potential self-ligations and simplifying library preparation procedures. AppOligos can be produced by chemical synthesis or enzymatic modification. However, adenylation via chemical synthesis is inefficient and expensive, while enzymatic modification requires pre-phosphorylated substrate and additional purification. Here we cloned and characterized the Pfu RNA ligase encoded by the PF0353 gene in the hyperthermophilic archaea Pyrococcus furiosus. We further engineered fusion enzymes containing both Pfu RNA ligase and T4 polynucleotide kinase. One fusion enzyme, 8H-AP, was thermostable and can directly catalyze 5′-OH-terminated DNA substrates to adenylated products. The newly discovered Pfu RNA ligase and the engineered fusion enzyme may be useful tools for applications using AppOligos.     

Division of labor within the DNA damage tolerance system reveals non-epistatic and clinically actionable targets for precision cancer medicine

Crosslink repair depends on the Fanconi anemia pathway and translesion synthesis polymerases that replicate over unhooked crosslinks. Translesion synthesis is regulated via ubiquitination of PCNA, and independently via translesion synthesis polymerase REV1. The division of labor between PCNA-ubiquitination and REV1 in interstrand crosslink repair is unclear. Inhibition of either of these pathways has been proposed as a strategy to increase cytotoxicity of platinating agents in cancer treatment. Here, we defined the importance of PCNA-ubiquitination and REV1 for DNA in mammalian ICL repair. In mice, loss of PCNA-ubiquitination, but not REV1, resulted in germ cell defects and hypersensitivity to cisplatin. Loss of PCNA-ubiquitination, but not REV1 sensitized mammalian cancer cell lines to cisplatin. We identify polymerase Kappa as essential in tolerating DNA damage-induced lesions, in particular cisplatin lesions. Polk-deficient tumors were controlled by cisplatin treatment and it significantly delayed tumor outgrowth and increased overall survival of tumor bearing mice. Our results indicate that PCNA-ubiquitination and REV1 play distinct roles in DNA damage tolerance. Moreover, our results highlight POLK as a critical TLS polymerase in tolerating multiple genotoxic lesions, including cisplatin lesions. The relative frequent loss of Polk in cancers indicates an exploitable vulnerability for precision cancer medicine.     

一种快速提取禽源性大肠埃希氏菌外胰蛋白的方法

介绍一种快速提取禽源性大肠埃希氏菌外膜蛋白的方法。该法是对Ｋａｐｕｒ等发表的方法的改进。全过程只需超速离心一次,比Ｋａｐｕｒ等的方法缩短了４ｈ。所得样品可直接用于禽源性大肠埃希氏菌外膜蛋白模式的测定。     

黔西北铅锌矿区植物群落分布及其对重金属的迁移特征

重金属耐性植物和超富集植物的筛选、鉴定和驯化是植物修复技术研究与发展的关键。以黔西北4个不同恢复年限的铅锌矿为研究对象,通过群落生态调查利用聚类分析方法筛选出研究区域中重金属耐性植物优势种,并分析其对重金属Pb、Zn、Cu、Cd的迁移富集能力。结果表明:4个矿区共发现高等植物22种,分属13科21属,筛选出9种重金属耐性植物优势种,其中转运系数大于1的植物有:黄花蒿(Cu)、珠光香青(Zn)、大叶醉鱼草(Zn/Pb/Cd)、野艾蒿(Cu/Zn/Pb/Cd);没有富集系数大于1的植物。其中大叶醉鱼草具有耐贫瘠、耐旱、生物量大等优势,可将其作为典型的重金属耐性先锋植物,用于矿区废弃地的植物修复。