Toxoplasma gondii α-amylase deletion mutant is a promising vaccine against acute and chronic toxoplasmosis

Individuals with inhibited immunity may develop lethal toxoplasmosis; thus, a safe and effective vaccine is urged to be developed. Toxoplasma gondii (T. gondii) α-amylase (α-AMY) is one of the enzymes responsible for starch digestion. In the present study, we first generated a ME49Δα-amy mutant and discovered that loss of α-AMY robustly grew in vitro but contributed to significant virulence attenuation in vivo. Therefore, we established a mouse model to explore the protective immunity of Δα-amy mutant against acute and chronic toxoplasmosis. The results indicated that the survival rates of short-term or long-term immunized mice re-infected with the tachyzoites of multiple T. gondii strains were nearly 100%. ME49Δα-amy not only could provide protective immunity against tachyzoites infection but also could resist the infection of tissue cysts. Furthermore, we detected that ME49Δα-amy vaccination could effectively eliminate the proliferation of parasites in mice and prevent the formation of cysts. The significant increases of Th1-type cytokines, Th2-type cytokines and specific total IgG and IgG subclasses (IgG2a and IgG1) confirmed efficiency of a combination of cellular and humoral immunity against infection. In conclusion, ME49Δα-amy attenuated strain can produce strong immune responses to provide efficient protection against toxoplasmosis, which signifies that ME49Δα-amy mutant may be a potential vaccine candidate.     

Increased miR‐34c mediates synaptic deficits by targeting synaptotagmin 1 through ROS‐JNK‐p53 pathway in Alzheimer’s Disease

Alzheimer's disease (AD) and cancer have inverse relationship in many aspects. Some tumor suppressors, including miR‐34c, are decreased in cancer but increased in AD. The upstream regulatory pathways and the downstream mechanisms of miR‐34c in AD remain to be investigated. The expression of miR‐34c was detected by RT–qPCR in oxidative stressed neurons, hippocampus of SAMP8 mice, or serum of patients with amnestic mild cognitive impairment (aMCI). Dual luciferase assay was performed to confirm the binding sites of miR‐34c in its target mRNA. The Morris water maze (MWM) was used to evaluate learning and memory in SAMP8 mice administrated with miR‐34c antagomir (AM34c). Golgi staining was used to evaluate the synaptic function and structure. The dramatically increased miR‐34c was mediated by ROS‐JNK‐p53 pathway and negatively regulated synaptotagmin 1 (SYT1) expression by targeting the 3′‐untranslated region (3′‐UTR) of syt1 in AD. The expression of SYT1 protein was reduced by over expression of miR‐34c in the HT‐22 cells and vice versa. Administration of AM34c by the third ventricle injection or intranasal delivery markedly increased the brain levels of SYT1 and ameliorated the cognitive function in SAMP8 mice. The serum miR‐34c was significantly increased in patients with aMCI and might be a predictive biomarker for diagnosis of aMCI. These results indicated that increased miR‐34c mediated synaptic and memory deficits by targeting SYT1 through ROS‐JNK‐p53 pathway and the miR‐34c/SYT1 pathway could be considered as a promising novel therapeutic target for patients with AD.     

Psoralen attenuates bleomycin‐induced pulmonary fibrosis in mice through inhibiting myofibroblast activation and collagen deposition

Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by excessive deposition of extracellular matrix (ECM) and chronic inflammation with limited therapeutic options. Psoralen, a major active component extracted from Psoralea corylifolia L. seed, has several biological effects. However, the role of psoralen in IPF is still unclear. Here, we hypothesized that psoralen played an essential role in IPF in the inhibition of fibroblast proliferation and inflammatory response. A murine model of IPF was established by injecting bleomycin (BLM) intratracheally, and psoralen was administered for 14 days from the 7^th to 21^st day after BLM injection. Our results demonstrated that psoralen treatment reduced body weight loss and improved the survival rate of mice with IPF. Histological and immunofluorescent examination showed that psoralen alleviated BLM‐induced lung parenchymal inflammatory and fibrotic alteration. Furthermore, psoralen inhibited proliferation and collagen synthesis of mouse fibroblasts and partially reversed BLM‐induced expression of α‐smooth muscle actin at both the tissue and cell level. Moreover, psoralen decreased the expression of transforming growth factor‐β1, interleukin‐1β, and tumor necrosis factor‐α in the lungs of BLM‐stimulated mice. Our results reveale for the first time that psoralen exerts therapeutic effects against IPF in a BLM‐induced murine model.     

Circular RNA hsa_circ_0085131 is involved in cisplatin‐resistance of non‐small‐cell lung cancer cells by regulating autophagy

Non‐small‐cell lung carcinoma (NSCLC) continues to top the list of cancer mortalities worldwide. The role of circular RNAs (circRNAs) in tumorigenesis has been increasingly appreciated, although it is relatively unexplored in NSCLC. Herein, we reported the role of hsa_circ_0085131 in NSCLC. In the present study, NSCLC tumor specimens exhibited a higher hsa_circ_0085131 level in comparison to para‐tumor samples. And the higher level of hsa_circ_0085131 was associated with recurrence and poorer survival of NSCLC. Moreover, hsa_circ_0085131 promoted cell proliferation and cisplatin (DDP)‐resistance. Furthermore, hsa_circ_0085131 regulated cell DDP‐resistance by modulating autophagy. Hsa_circ_0085131 acted as a competing endogenous RNA of miR‐654‐5p to release autophagy‐associated factor ATG7 expression, thereby promoting cell chemoresistance. In conclusion, hsa_circ_0085131 enhances DDP‐resistance of NSCLC cells through sequestering miR‐654‐5p to upregulate ATG7, leading to cell autophagy. Therefore, these findings advocate targeting the hsa_circ_0085131/miR‐654‐5p/ATG7 axis as a potential therapeutic option for patients with NSCLC who are resistant to DDP.     

The impacts of warming and nitrogen addition on competitive ability of native and invasive populations of Plantago virginica

全球变化因子(如增温和氮沉降)可能会影响生物入侵,但是这些因子如何影响入侵物种的表现并进一步调节入侵物种与本地竞争者之间的相互作用仍不清楚。本文通过为期五个月的温室实验,研究了增温(开顶式增温箱,+0.62°C)和氮添加(4.2 g N m⁻²)对入侵物种北美 车前(Plantago virginica)原产地和入侵地种群与本地车前草(Plantago asiatica)竞争的影响。实验结果表明,在增温及其与氮添加处理(W × N) 的相互作用下,P. virginica的入侵种群(PV-In)和原产地种群(PV-Na)在与本地竞争者P. asiatica竞争时具有不同的生物量分配策略。其中,PV-Na在与P. asiatica竞争时增加了地下生物量,而PV-In增加了地上生物量。我们还发现,P. virginica对增温和氮添加比P. asiatica的反应更强 烈。增温显著降低了P. virginica的竞争能力,这表明P. virginica比P. asiatica对增温的响应更为敏感。同样,在竞争条件下,氮添加及 其和增温交互作用减少了PV-In地下生物量,但增加了PV-Na地上和总生物量。这些发现表明,P. virginica在入侵过程中改变了生物量分配 策略,PV-In展示出更具弹性的竞争能力以适应环境变化(特别是增温)。这些发现可能有助于我们预测气候变化下的植物入侵并制定相应的 管理策略。     

中国兽类一新纪录白尾高山䶄及西藏、湖北和四川兽类各一省级新纪录

在最近几年开展的小型兽类调查和研究中,通过形态学和分子鉴定的方法,证实在新疆发现的白尾高山䶄（Alticola albicauda True, 1894）是中国新纪录。该种尾全白色,末端有白色毛束;身体背部淡红褐色,腹部纯白。在基于Cyt b构建的系统树中和GenBank中的白尾高山䶄聚在一起,并与银色高山䶄（Alticola argentatus Severtzov,1879）形成姊妹群,两者间遗传距离为5%;在西藏发现小毛足鼠（Phodopus roborovskii Satunin,1902）,其特征和我国其他区域分布的小毛足鼠一致,两者之间Cyt b基因遗传距离（K2P）为0.6%,是西藏新纪录;在四川发现丽江绒鼠（Eothenomys fidelis Hinton, 1923）,牙齿特征,尾长和体长之比和地模标本基本一致,但个体较小,在基于Cyt b构建的系统发育树显示,四川标本为独立分支,表明形态和分子上均存在一定的分化,但和地模标本的遗传 距离只有1.1%,应为同一种,为四川省新纪录;在湖北发现循化鼠兔（Ochotona xunhuaensis Sou and Feng, 1984）,有异耳屏,头骨较扁平,符合循化鼠兔的鉴定特征,与模式产地的循化鼠兔Cyt b基因的遗传距离为1.9%,为湖北新纪录。