Monophosphoryl lipid A alleviated radiation-induced testicular injury through TLR4-dependent exosomes

Radiation protection on male testis is an important task for ionizing radiation-related workers or people who receive radiotherapy for tumours near the testicle. In recent years, Toll-like receptors (TLRs), especially TLR4, have been widely studied as a radiation protection target. In this study, we detected that a low-toxicity TLR4 agonist monophosphoryl lipid A (MPLA) produced obvious radiation protection effects on mice testis. We found that MPLA effectively alleviated testis structure damage and cell apoptosis induced by ionizing radiation (IR). However, as the expression abundance differs a lot in distinct cells and tissues, MPLA seemed not to directly activate TLR4 singling pathway in mice testis. Here, we demonstrated a brand new mechanism for MPLA producing radiation protection effects on testis. We observed a significant activation of TLR4 pathway in macrophages after MPLA stimulation and identified significant changes in macrophage-derived exosomes protein expression. We proved that after MPLA treatment, macrophage-derived exosomes played an important role in testis radiation protection, and specially, G-CSF and MIP-2 in exosomes are the core molecules in this protection effect.     

Microtubule-assisted mechanism for toxisome assembly in Fusarium graminearum

In Fusarium graminearum, a trichothecene biosynthetic complex known as the toxisome forms ovoid and spherical structures in the remodelled endoplasmic reticulum (ER) under mycotoxin-inducing conditions. Previous studies also demonstrated that disruption of actin and tubulin results in a significant decrease in deoxynivalenol (DON) biosynthesis in F. graminearum. However, the functional association between the toxisome and microtubule components has not been clearly defined. In this study we tested the hypothesis that the microtubule network provides key support for toxisome assembly and thus facilitates DON biosynthesis. Through fluorescent live cell imaging, knockout mutant generation, and protein–protein interaction assays, we determined that two of the four F. graminearum tubulins, α₁ and β₂ tubulins, are indispensable for DON production. We also showed that these two tubulins are directly associated. When the α₁–β₂ tubulin heterodimer is disrupted, the metabolic activity of the toxisome is significantly suppressed, which leads to significant DON biosynthesis impairment. Similar phenotypic outcomes were shown when F. graminearum wild type was treated with carbendazim, a fungicide that binds to microtubules and disrupts spindle formation. Based on our results, we propose a model where α₁–β₂ tubulin heterodimer serves as the scaffold for functional toxisome assembly in F. graminearum.     

Strigolactone mimic 2-nitrodebranone is highly active in Arabidopsis growth and development

Strigolactones play crucial roles in regulating plant architecture and development, as endogenous hormones, and orchestrating symbiotic interactions with fungi and parasitic plants, as components of root exudates. rac-GR24 is currently the most widely used strigolactone analog and serves as a reference compound in investigating the action of strigolactones. In this study, we evaluated a suite of debranones and found that 2-nitrodebranone (2NOD) exhibited higher biological activity than rac-GR24 in various aspects of plant growth and development in Arabidopsis, including hypocotyl elongation inhibition, root hair promotion and senescence acceleration. The enhanced activity of 2NOD in promoting AtD14–SMXL7 and AtD14–MAX2 interactions indicates that the molecular structure of 2NOD is a better match for the ligand perception site pocket of D14. Moreover, 2NOD showed lower activity than rac-GR24 in promoting Orobanche cumana seed germination, suggesting its higher ability to control plant architecture than parasitic interactions. In combination with the improved stability of 2NOD, these results demonstrate that 2NOD is a strigolactone analog that can specifically mimic the activity of strigolactones and that 2NOD exhibits strong potential as a tool for studying the strigolactone signaling pathway in plants.     

Upregulation of P53 promotes nucleus pulposus cell apoptosis in intervertebral disc degeneration through upregulating NDRG2

P53 is an apoptosis marker which is involved in determining nucleus pulposus (NP) cell fate. Little is known about P53 interaction with N-Myc downstream-regulated gene 2 (NDRG2) in intervertebral disc degeneration (IVDD). Here, we studied the role of the P53-NDRG2 axis in IVDD. We found that NDRG2 was expressed in NP tissue obtained from patients with IVDD. The level of NDRG2 was positively related to the severity of IVDD, as determined by Pfirrmann grading. Subsequently, we overexpressed NDRG2 in human NP cells by adenoviral transfection and studied the effects of increased levels of NDRG2 on the viability and apoptosis of these cells. NDRG2 overexpression induced NP cell apoptosis and reduced viability in NP cells obtained from patient with IVDD. We also found that the level of P53 was elevated in NP cells from patients with IVDD and treatment with exogenous P53 upregulated NDRG2 in NP cells. Last, IVDD model was established in P53 knockout mice and the pathological changes in the intervertebral discs and NDRG2 expression were examined. P53 knockout can reduce the damage of NP tissues after IVDD surgery to some extent. Restoration of NDRG2 antagonized the effect of P53 knockout on IVDD. Collectively, this study suggests that elevated P53 in NP cells stimulates apoptosis of the cells by upregulating NDRG2 expression, thereby exacerbating IVDD.     

Natural enemies of herbivores maintain their biological control potential under short‐term exposure to future CO2, temperature,and precipitation patterns

Climate change will profoundly alter the physiology and ecology of plants, insect herbivores, and their natural enemies, resulting in strong effects on multitrophic interactions. Yet, manipulative studies that investigate the direct combined impacts of changes in CO₂, temperature, and precipitation on the third trophic level remain rare. Here, we assessed how exposure to elevated CO₂, increased temperature, and decreased precipitation directly affect the performance and predation success of species from four major groups of herbivore natural enemies: an entomopathogenic nematode, a wolf spider, a ladybug, and a parasitoid wasp. A four‐day exposure to future climatic conditions (RCP 8.5), entailing a 28% decrease in precipitation, a 3.4°C raise in temperature, and a 400 ppm increase in CO₂ levels, slightly reduced the survival of entomopathogenic nematodes, but had no effect on the survival of other species. Predation success was not negatively affected in any of the tested species, but it was even increased for wolf spiders and entomopathogenic nematodes. Factorial manipulation of climate variables revealed a positive effect of reduced soil moisture on nematode infectivity, but not of increased temperature or elevated CO₂. These results suggest that natural enemies of herbivores may be well adapted to short‐term changes in climatic conditions. These findings provide mechanistic insights that will inform future efforts to disentangle the complex interplay of biotic and abiotic factors that drive climate‐dependent changes in multitrophic interaction networks.     

绿盖粉孢牛肝菌中一个新的甾体糖苷

从绿盖粉孢牛肝菌（Tylopilus virens）中分离得到一个新的麦角甾烷型甾体糖苷,其化学结构通过波谱学方法鉴定为：（22E,24R）-麦角甾-7,22-二烯-5α,6β-二醇-3β-O-[3-（3-苯基丙酰氧基）]-β-D-葡萄吡喃糖苷,命名为tylopiloside（1）,同时,其苷元cerevisterol（2）也从该菌中分离得到。值得注意的是,这种糖片段上有芳环取代的烷酰氧基基团的麦角甾烷型甾体糖苷为真菌中首次报道。     

Taurine replacement attenuates hyperalgesia and abnormal calcium signaling in sensory neurons of STZ-D rats

The etiology of painful diabetic neuropathy is poorly understood, but may result from neuronal hyperexcitability secondary to alterations of Ca2+ signaling in sensory neurons. The naturally occurring amino acid taurine functions as an osmolyte, antioxidant, Ca2+ modulator, inhibitory neurotransmitter, and analgesic such that its depletion in diabetes may predispose one to neuronal hyperexcitability and pain. This study reports the effects of taurine replacement on hyperalgesia and sensory neuron Ca2+ homeostasis in streptozotocin-diabetic (STZ-D) rats. Nondiabetic and STZ-D rats were treated with a 2% taurine-supplemented diet for 6-12 wk. Thermal hyperalgesia and mechanical allodynia were determined by measuring hindpaw withdrawal latency to radiant heat and the withdrawal threshold to the von Frey anesthesiometer. Intracellular Ca2+ signaling was explored in neurons from L4-L6 dorsal root ganglia (DRG), using fura 2 fluorescence. Taurine replacement of diabetic rats attenuated deficits of nerve conduction and prevented reductions of mechanical and thermal withdrawal threshold and latency, respectively. In small DRG sensory neurons from diabetic rats, recovery of intracellular Ca2+ concentration ([Ca2+]i) in response to KCl was slowed and 73% corrected by taurine. The amplitudes of caffeine and ATP-induced [Ca2+]i transients were decreased by 47 and 27% (P < 0.05), respectively, in diabetic rat DRG sensory neurons and corrected by 74 and 93% (P < 0.05), respectively, by taurine replacement. These data indicate that taurine is important in the regulation of neuronal Ca2+ signaling and that taurine deficiency may predispose one to nerve hyperexcitability and pain, complicating diabetes.     

Risks of Biological Invasion on the Belt and Road

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甘南高山林线岷江冷杉—杜鹃种群结构与动态

高山林线是一种典型的生态交错带,是对气候反映最敏感的地区之一。甘肃南部高山林线区域主要以原始岷江冷杉种群和杜鹃种群为优势种,通过对岷江冷杉和杜鹃种群建立静态生命表,绘制存活曲线描述其结构特征,利用种群数量动态预测时间序列分析定量研究未来的发展趋势。结果显示:(1)岷江冷杉种群幼苗比较丰富,能很好的维持种群个体的自疏死亡,存活曲线呈Deevey-Ⅲ型;杜鹃种群幼苗缺乏,存活曲线趋向于Deevey-Ⅰ型;死亡曲线和危险率曲线都随着龄级的增加而增加,杜鹃种群的死亡率在各个龄级一直大于岷江冷杉种群,危险率在Ⅱ龄级以后杜鹃种群也始终大于岷江冷杉种群。(2)岷江冷杉种群结构动态变化指数Vpi大于修正后的种群结构动态变化指数V′pi且大于0,而杜鹃种群结构动态变化指数Vpi小于修正后的种群结构动态变化指数V′pi且小于0,则岷江冷杉种群属于增长型,杜鹃种群属于衰退型,岷江冷杉、杜鹃随机干扰极大值分别为0.027、0.011,说明二者对外界干扰均比较敏感。(3)杜鹃种群时间序列预测为前期幼苗比较缺乏,中期稳定,后期衰退的动态特征,而岷江冷杉种群表现出各龄级时间变化较小,幼苗个体数较多,种群为稳定增长型,岷江冷杉更能适应甘肃南部高山林线区域当前环境。