Human Monoclonal Antibodies: On the Menu of Targeted Therapeutics Against COVID-19

Virologica Sinica - Coronavirus disease 2019 (COVID-19), reminiscent of the severe acute respiratory syndrome (SARS) outbreak in 2003, has been a tragic disaster to people all over the world. As...     

不同农药对木瓜秀粉蚧的毒力及复配增效作用

为筛选对入侵害虫木瓜秀粉蚧毒力较好的农药及复配增效配比,为该虫的化学药剂防治提供理论依据,本文采用叶面喷雾法测定了11种农药对木瓜秀粉蚧2龄若虫的室内毒力,挑选毒力较好的两种药剂进行复配,筛选增效配比,并进行田间药效试验。结果表明,11种农药对木瓜秀粉蚧的毒力大小依次为:螺螨酯>哒螨灵>噻虫胺>联苯菊酯>矿物油>高效氯氰菊酯>炔螨特>啶虫脒>吡虫啉>噻螨酮>四螨嗪。哒螨灵与螺螨酯(60∶40)复配共毒系数最大,为182.47。田间药效试验发现,混配药剂防效均高于单剂且达到差异显著。     

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。