Tillering and small grain 1 dominates the tryptophan aminotransferase family required for local auxin biosynthesis in rice

Auxin is a crucial phytohormone, controlling multiple aspects of plant growth and responses to the changing environment. However, the role of local auxin biosynthesis in specific developmental programs remains unknown in crops. This study characterized the rice tillering and small grain 1 (tsg1) mutant, which has more tillers but a smaller panicle and grain size resulting from a reduction in endogenous auxin. TSG1 encodes a tryptophan aminotransferase that is allelic to the FISH BONE (FIB) gene. The tsg1 mutant showed hypersensitivity to indole‐3‐acetic acid and the competitive inhibitor of aminotransferase, L‐kynurenine. TSG1 knockout resulted in an increased tiller number but reduction in grain number and size, and decrease in height. Meanwhile, deletion of the TSG1 homologs OsTAR1, OsTARL1, and OsTARL2 caused no obvious changes, although the phenotype of the TSG1/OsTAR1 double mutant was intensified and infertile, suggesting gene redundancy in the rice tryptophan aminotransferase family. Interestingly, TSG1 and OsTAR1, but not OsTARL1 and OsTARL2, displayed marked aminotransferase activity. Meanwhile, subcellular localization was identified as the endoplasmic reticulum, while phylogenetic analysis revealed functional divergence of TSG1 and OsTAR1 from OsTARL1 and OsTARL2. These findings suggest that TSG1 dominates the tryptophan aminotransferase family, playing a prominent role in local auxin biosynthesis in rice.     

Colonization of endophyte Acremonium sp. D212 in Panax notoginseng and rice mediated by auxin and jasmonic acid

Endophytic fungi can be beneficial to plant growth. However, the molecular mechanisms underlying colonization of Acremonium spp. remain unclear.In this study, a novel endophytic Acremonium strain was isolated from the buds of Panax notoginseng and named Acremonium sp. D212. The Acremonium sp. D212 could colonize the roots of P. notoginseng,enhance the resistance of P. notoginseng to root rot disease, and promote root growth and saponin biosynthesis in P. notoginseng. Acremonium sp. D212 could secrete indole-3-acetic acid(IAA) and jasmonic acid(JA), and inoculation with the fungus increased the endogenous levels of IAA and JA in P. notoginseng. Colonization of the Acremonium sp. D212 in the roots of the rice line Nipponbare was dependent on the concentration of methyl jasmonate(Me JA)(2–15 μmol/L) and 1-naphthalenacetic acid(NAA)(10–20 μmol/L). Moreover, the roots of the JA signaling-defective coi1-18 mutant were colonized by Acremonium sp. D212 to a lesser degree than those of the wild-type Nipponbare and mi R393 boverexpressing lines, and the colonization was rescued by Me JA but not by NAA. It suggests that the cross-talk between JA signaling and the auxin biosynthetic pathway plays a crucial role in the colonization of Acremonium sp. D212 in host plants.     

Tumour‐associated macrophages as a novel target of VEGI‐251 in cancer therapy

Tumour‐associated macrophages (TAMs), which possess M2‐like characters and are derived from immature monocytes in the circulatory system, represent a predominant population of inflammatory cells in solid tumours. TAM infiltration in tumour microenvironment can be used as an important prognostic marker in many cancer types and is a potential target for cancer prevention or treatment. VEGI‐251 not only is involved in the inhibition of tumour angiogenesis, but also participates in the regulation of host immunity. This work aimed to investigate the involvement of VEGI‐251 in the regulation of specific antitumour immunity. We found that recombinant human VEGI‐251(rhVEGI‐251) efficiently mediated the elimination of TAMs in tumour tissue in mice, and induced apoptosis of purified TAMs in vitro. During this process, caspase‐8 and caspase‐3 were activated, leading to PARP cleavage and apoptosis. Most importantly, we further elucidated the mechanism underlying VEGI‐251‐triggered TAM apoptosis, which suggests that ASK1, an intermediate component of the VEGI‐251, activates the JNK pathway via TRAF2 in a potentially DR3‐dependent manner in the process of TAM apoptosis. Collectively, our findings provide new insights into the basic mechanisms underlying the actions of VEGI‐251 that might lead to future development of antitumour therapeutic strategies using VEGI‐251 to target TAMs.     

Long non-coding RNA FEZF1-AS1 induced progression of ovarian cancer via regulating miR-130a-5p/SOX4 axis

Emerging studies have revealed the critical role of long non-coding RNAs (lncRNAs) in epithelial ovarian cancer (EOC) development and progression. Till now, the roles and potential mechanisms regarding FEZF1 antisense RNA 1 (FEZF1-AS1) within ovarian cancer (OC) remain unclear. The objective of this study was to uncover the biological function and the underlying mechanism of LncRNA FEZF1-AS1 in OC progression. FEZF1-AS1 expression levels were studied in cell lines and tissues of human ovarian cancer. In vitro studies were performed to evaluate the impact of FEZF1-AS1 knock-down on the proliferation, invasion, migration and apoptosis of OC cells. Interactions of FEZF1-AS1 and its target genes were identified by luciferase reporter assays. Our data showed overexpression of FEZF1-AS1 in OC cell lines and tissues. Cell migration, proliferation, invasion, wound healing and colony formation were suppressed by silencing of FEZF1-AS1. In contrast, cell apoptosis was promoted by FEZF1-AS1 knock-down in vitro. Furthermore, online bioinformatics analysis and tools suggested that FEZF1-AS1 directly bound to miR-130a-5p and suppressed its expression. Moreover, the inhibitory effects of miR-130a-5p on the OC cell growth were reversed by FEZF1-AS1 overexpression, which was associated with the increase in SOX4 expression. In conclusion, our results revealed that FEZF1-AS1 promoted the metastasis and proliferation of OC cells by targeting miR-130a-5p and its downstream SOX4 expression.     

A new trick for an old dog: The application of mifepristone in the treatment of adenomyosis

Adenomyosis is also called internal endometriosis and affects about 20% of reproductive‐aged women. It seriously reduces life quality of patients because current drug therapies face with numerous challenges. Long‐term clinical application of mifepristone exhibits wonderful therapeutic effects with mild side‐effects in many disorders since 1982. Since adenomyosis is a refractory disease, we investigate whether mifepristone can be applied in the treatment of adenomyosis. In this study, we investigated the direct effects of mifepristone on human primary eutopic endometrial epithelial cells and stromal cells in adenomyosis. We found that mifepristone causes cell cycle arrest through inhibiting CDK1 and CDK2 expressions and induces cell apoptosis via the mitochondria‐dependent signalling pathway in endometrial epithelial cells and stromal cells of adenomyosis. Furthermore, mifepristone inhibits the migration of endometrial epithelial cells and stromal cells through decreasing CXCR4 expression and restricts the invasion of endometrial epithelial cells via suppression of epithelial‐mesenchymal transition in adenomyosis. We also found that mifepristone treatment decreases the uterine volume, CA125 concentration and increases the haemoglobin concentration in serum for adenomyosis patients. Therefore, we demonstrate that mifepristone could serve as a novel therapeutic drug in the treatment of adenomyosis, and therefore, the old dog can do a new trick.     

Endothelial S1pr1 regulates pressure overload‐induced cardiac remodelling through AKT‐eNOS pathway

Cardiac vascular microenvironment is crucial for cardiac remodelling during the process of heart failure. Sphingosine 1‐phosphate (S1P) tightly regulates vascular homeostasis via its receptor, S1pr1. We therefore hypothesize that endothelial S1pr1 might be involved in pathological cardiac remodelling. In this study, heart failure was induced by transverse aortic constriction (TAC) operation. S1pr1 expression is significantly increased in microvascular endothelial cells (ECs) of post‐TAC hearts. Endothelial‐specific deletion of S1pr1 significantly aggravated cardiac dysfunction and deteriorated cardiac hypertrophy and fibrosis in myocardium. In vitro experiments demonstrated that S1P/S1pr1 praxis activated AKT/eNOS signalling pathway, leading to more production of nitric oxide (NO), which is an essential cardiac protective factor. Inhibition of AKT/eNOS pathway reversed the inhibitory effect of EC‐S1pr1‐overexpression on angiotensin II (AngII)‐induced cardiomyocyte (CM) hypertrophy, as well as on TGF‐β‐mediated cardiac fibroblast proliferation and transformation towards myofibroblasts. Finally, pharmacological activation of S1pr1 ameliorated TAC‐induced cardiac hypertrophy and fibrosis, leading to an improvement in cardiac function. Together, our results suggest that EC‐S1pr1 might prevent the development of pressure overload‐induced heart failure via AKT/eNOS pathway, and thus pharmacological activation of S1pr1 or EC‐targeting S1pr1‐AKT‐eNOS pathway could provide a future novel therapy to improve cardiac function during heart failure development.     

不同目标力线设定对开放性楔形胫骨高位截骨术治疗膝关节骨性关节炎疗效的影响

目的:探讨开放性楔形胫骨高位截骨术(OWHTO)中采用不同目标力线对单间室膝关节骨性关节炎(KOA)疗效的影响。方法:回顾性分析本院收治的2016年9月～2018年9月采用OWHTO治疗单间室KOA患者41例的临床资料,根据不同目标力线分为固定力线组和个体化力线组,固定力线组19例患者采用统一调目标力线至Fujisawa点治疗,个体化力线组22例根据术中关节软骨Outerbridge分级、个体化调定目标力线治疗,对比两组术前及术后1.5个月、3个月、6个月、12个月的疼痛视觉模拟评分(VAS)及美国特种外科医院膝关节(HSS)评分变化,并对比术前和12个月时MRI及关节镜影像。结果:术后所有患者VAS评分、HSS评分均较术前改善(P0.05),其中个体化力线组术后1.5个月、3个月时VAS评分优于固定力线组,差异有统计学意义(P0.05)。MRI及关节镜显示两组患者均有不同程度软骨再生。结论:采用OWHTO治疗单间室KOA,根据患者不同软骨磨损情况制定个体化目标力线方案有利于患者早期疼痛的改善,但其长期功能的恢复及软骨再生与固定力线方案无明显差异。     

Allotransplantation of adult spinal cord tissues after complete transected spinal cord injury: Long-term survival and functional recovery in canines

Science China Life Sciences - Spinal cord injury (SCI), especially complete transected SCI, leads to loss of cells and extracellular matrix and functional impairments. In a previous study, we...     

GPI7-mediated glycosylphosphatidylinositol anchoring regulates appressorial penetration and immune evasion during infection of Magnaporthe oryzae

Glycosylphosphatidylinositol (GPI) anchoring plays key roles in many biological processes by targeting proteins to the cell wall; however, its roles are largely unknown in plant pathogenic fungi. Here, we reveal the roles of the GPI anchoring in Magnaporthe oryzae during plant infection. The GPI-anchored proteins were found to highly accumulate in appressoria and invasive hyphae. Disruption of GPI7, a GPI anchor-pathway gene, led to a significant reduction in virulence. The Δgpi7 mutant showed significant defects in penetration and invasive growth. This mutant also displayed defects of the cell wall architecture, suggesting GPI7 is required for cell wall biogenesis. Removal of GPI-anchored proteins in the wild-type strain by hydrofluoric acid (HF) pyridine treatment exposed both the chitin and β-1,3-glucans to the host immune system. Exposure of the chitin and β-1,3-glucans was also observed in the Δgpi7 mutant, indicating GPI-anchored proteins are required for immune evasion. The GPI anchoring can regulate subcellular localization of the Gel proteins in the cell wall for appressorial penetration and abundance of which for invasive growth. Our results indicate the GPI anchoring facilitates the penetration of M. oryzae into host cells by affecting the cell wall integrity and the evasion of host immune recognition.