Lectin receptor kinase OsLecRK‐S.7 is required for pollen development and male fertility

Pollen grains are covered by exine that protects the pollen from stress and facilitates pollination. Here we isolated a male sterile mutant s13283 in rice exhibiting aborted pollen with abnormal exine and defective aperture. The mutant gene encodes a novel plasma membrane‐localized legume‐lectin receptor kinase that we named OsLecRK‐S.7. OsLecRK‐S.7 was expressed at different levels in all tested tissues and throughout anther development. In vitro kinase assay showed OsLecRK‐S.7 capable of autophosporylation. Mutation in s13283 (E560K) and mutation of the conserved ATP binding site (K418E) both knocked out the kinase activity. Mass spectrometry showed Thr₃₇₆, Ser₃₇₈, Thr₃₈₆, Thr₄₀₃, and Thr₆₅₇ to be the autophosphorylation sites. Mutation of individual autophosphorylation site affected the in vitro kinase activity to different degrees, but did not abolish the gene function in fertility complementation. oslecrk‐s.7 mutant plant overexpressing OsLecRK‐S.7 recovered male fertility but showed severe growth retardation with reduced number of tillers, and these phenotypes were abolished by E560K or K418E mutation. The results indicated that OsLecRK‐S.7 was a key regulator of pollen development.     

Application of germ-free NOD-scid IL2rgnull mice as a humanized model for tumor microbiome precision medicine

正In 2013, tumor immunotherapy topped the list of the top ten scientific breakthroughs(Couzin-Frankel, 2013), and it was widely used in the treatment of lung cancer, kidney cancer,and melanoma(Routy et al., 2018). However, the response rate of patients to tumor immunotherapy varies, and usually,only a small percentage of patients respond well to treatment(Sambi et al., 2019).     

Inhibition of cyclooxygenase-2 enhanced intestinal epithelial homeostasis via suppressing β-catenin signalling pathway in experimental liver fibrosis

The intestinal barrier dysfunction is crucial for the development of liver fibrosis but can be disturbed by intestinal chronic inflammation characterized with cyclooxygenase-2 (COX-2) expression. This study focused on the unknown mechanism by which COX-2 regulates intestinal epithelial homeostasis in liver fibrosis. The animal models of liver fibrosis induced with TAA were established in rats and in intestinal epithelial–specific COX-2 knockout mice. The impacts of COX-2 on intestinal epithelial homeostasis via suppressing β-catenin signalling pathway were verified pharmacologically and genetically in vivo. A similar assumption was tested in Ls174T cells with goblet cell phenotype in vitro. Firstly, disruption of intestinal epithelial homeostasis in cirrhotic rats was ameliorated by celecoxib, a selective COX-2 inhibitor. Then, β-catenin signalling pathway in cirrhotic rats was associated with the activation of COX-2. Furthermore, intestinal epithelial–specific COX-2 knockout could suppress β-catenin signalling pathway and restore the disruption of ileal epithelial homeostasis in cirrhotic mice. Moreover, the effect of COX-2/PGE2 was dependent on the β-catenin signalling pathway in Ls174T cells. Therefore, inhibition of COX-2 may enhance intestinal epithelial homeostasis via suppression of the β-catenin signalling pathway in liver fibrosis.     

Protective impacts of household-based tuberculosis contact tracing are robust across endemic incidence levels and community contact patterns

There is an emerging consensus that achieving global tuberculosis control targets will require more proactive case finding approaches than are currently used in high-incidence settings. Household contact tracing (HHCT), for which households of newly diagnosed cases are actively screened for additional infected individuals is a potentially efficient approach to finding new cases of tuberculosis, however randomized trials assessing the population-level effects of such interventions in settings with sustained community transmission have shown mixed results. One potential explanation for this is that household transmission is responsible for a variable proportion of population-level tuberculosis burden between settings. For example, transmission is more likely to occur in households in settings with a lower tuberculosis burden and where individuals mix preferentially in local areas, compared with settings with higher disease burden and more dispersed mixing. To better understand the relationship between endemic incidence levels, social mixing, and the impact of HHCT, we developed a spatially explicit model of coupled household and community transmission. We found that the impact of HHCT was robust across settings of varied incidence and community contact patterns. In contrast, we found that the effects of community contact tracing interventions were sensitive to community contact patterns. Our results suggest that the protective benefits of HHCT are robust and the benefits of this intervention are likely to be maintained across epidemiological settings.     

Azetidines and spiro azetidines as novel P2 units in hepatitis C virus NS3 protease inhibitors

Herein, we report the synthesis and structure–activity relationship studies of new analogs of boceprevir 1 and telaprevir 2. Introduction of azetidine and spiroazetidines as a P2 substituent that replaced the pyrrolidine moiety of 1 and 2 led to the discovery of a potent hepatitis C protease inhibitor 37c (EC₅₀ = 0.8 μM).     

不同修复措施对黄河源退化高寒草甸植物群落与土壤养分的影响

为了揭示退化高寒草甸逆向转变的驱动因子,通过野外调查和室内分析相结合的方法探究了黄河源不同修复措施(施有机肥F、免耕补播N、施有机肥+免耕补播FN)处理高寒草甸植物群落特征、土壤理化性质和两者相关性的变化规律,阐明不同修复措施对黄河源退化高寒草甸植物群落与土壤养分的影响。结果表明：免耕补播显著增加草甸物种丰富度指数(P<0.05);施有机肥+免耕补播显著增加草甸植物盖度、总生物量、Shannon Wiener多样性指数和Pielous均匀度指数(P<0.05)。不同人工修复后草甸植物功能群地上、地下生物量变化趋势基本一致(除豆科)。和对照相比,莎草科,杂类草地上和地下生物量含量在N、FN处理分别降低83.04%、73.86%、30.43%、92.37%和96.51%、84.09%、85.68%、95.36%;禾本科地上和地下生物量含量在F、N和FN处理分别增加7.29%、23.45%、17.93%和6.04%、4.03%、10.52%;豆科地上生物量含量基本保持不变,地下生物量含量在F、N和FN处理分别降低24.43%、82.19%和42.61%。F显著增加土壤有机碳含量(...     

Hormetic Effect of Berberine Attenuates the Anticancer Activity of Chemotherapeutic Agents

Hormesis is a phenomenon of biphasic dose response characterized by exhibiting stimulatory or beneficial effects at low doses and inhibitory or toxic effects at high doses. Increasing numbers of chemicals of various types have been shown to induce apparent hormetic effect on cancer cells. However, the underlying significance and mechanisms remain to be elucidated. Berberine, one of the major active components of Rhizoma coptidis, has been manifested with notable anticancer activities. This study aims to investigate the hormetic effect of berberine and its influence on the anticancer activities of chemotherapeutic agents. Our results demonstrated that berberine at low dose range (1.25 ~ 5 μM) promoted cell proliferation to 112% ~170% of the untreated control in various cancer cells, while berberine at high dose rage (10 ~ 80 μM) inhibited cell proliferation. Further, we observed that co-treatment with low dose berberine could significantly attenuate the anticancer activity of chemotherapeutic agents, including fluorouracil (5-FU), camptothecin (CPT), and paclitaxel (TAX). The hormetic effect and thereby the attenuated anticancer activity of chemotherapeutic drugs by berberine may attributable to the activated protective stress response in cancer cells triggered by berberine, as evidenced by up-regulated MAPK/ERK1/2 and PI3K/AKT signaling pathways. These results provided important information to understand the potential side effects of hormesis, and suggested cautious application of natural compounds and relevant herbs in adjuvant treatment of cancer.