Duvelisib attenuates bleomycin-induced pulmonary fibrosis via inhibiting the PI3K/Akt/mTOR signalling pathway

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that seriously threatens the health of patients. The pathogenesis of IPF is still unclear, and there is a lack of effective therapeutic drugs. Myofibroblasts are the main effector cells of IPF, leading to excessive deposition of extracellular matrix (ECM) and promoting the progression of fibrosis. Inhibiting the excessive activation and relieving autophagy blockage of myofibroblasts is the key to treat IPF. PI3K/Akt/mTOR pathway plays a key regulatory role in promoting fibroblast activation and autophagy inhibition in lung fibrosis. Duvelisib is a PI3K inhibitor that can simultaneously inhibit the activities of PI3K-δ and PI3K-γ, and is mainly used for the treatment of relapsed/refractory chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma tumour (SLL). In this study, we aimed to examine the effects of Duvelisib on pulmonary fibrosis. We used a mouse model of bleomycin-induced pulmonary fibrosis to evaluate the effects of Duvelisib on pulmonary fibrosis in vivo and further explored the potential pharmacological mechanisms of Duvelisib in lung fibroblasts in vitro. The in vivo experiments showed that Duvelisib significantly alleviated bleomycin-induced collagen deposition and improved pulmonary function. In vitro and in vivo pharmacological experiments showed that Duvelisib dose-dependently suppressed lung fibroblast activation and improved autophagy inhibition by inhibiting the phosphorylation of PI3K, Akt and mTOR. Our results indicate that Duvelisib can alleviate the severity of pulmonary fibrosis and provide potential drugs for the treatment of pulmonary fibrosis.     

春小麦对骤旱的响应特征及其阈值分析

与缓慢发展的干旱过程不同,骤旱具有发生速度快,短期内可致害的特点。目前,关于作物骤旱致害的临界阈值及其调控机制尚不清楚。以春小麦为供试作物,通过桶栽试验,模拟研究骤旱过程中小麦受旱致害的过程特征及其控制因素。结果发现,发生骤旱时土壤含水量下降呈先快后慢的变化趋势,叶片水分和叶水势则呈先慢后快的指数变化趋势。叶片光合生理指标对土壤水分的下降存在明显的阈值响应,且不同生理指标的阈值并不完全相同,其中净光合速率与表征叶片光合能力的指标（最大羧化速率）对土壤有效含水量的响应阈值为0.4,气孔导度和蒸腾速率对土壤有效含水量的响应阈值分别为0.5和0.4。而小麦光合生理指标对叶片水分和叶水势的阈值响应并不明显。同时依据各生理指标相关和通径分析结果得出,骤旱发生时引起小麦叶片净光合速率快速降低的主导因子为非气孔因素,而并不是以往作物受旱研究中的气孔因素。本研究结果有望丰富干旱影响认知,并可为科学应对干旱提供依据。     

浙西早寒武世梅树村期棒状化石

该文记述了浙江省西部江山县新塘坞地区灯影组(梅树村期)中新发现的矿化骨骼化石——浙江棒(新属)Zhejiangorhabdion gen.nov.。该化石的形态与以往化石类群均不相同,为个体微小的棒状,表面具较复杂的纹饰,不同个体间的纹饰都有一定变化,推测是动物体内不同部位的骨棒所具有的特征,代表了一个新的化石类群。新属的发现丰富了梅树村期动物群的内容,对了解具骨骼动物群体在这一时期的演化具有一定的意义。     

Regulation of estrogen receptor protein and messenger ribonucleic acid by estradiol and progesterone in rat uterus

The objective of this study was to examine the mechanisms of estrogen receptor (ER) processing and replenishment in the uterus of ovariectomized rats after estradiol and progesterone treatment. Uterine ER binding activity, ER protein and ER mRNA were measured by receptor binding exchange assay, Western blot and slot blot, respectively. The regulation of ER levels in rat uterus by estradiol and progesterone was very dramatic. Changes in ER protein were faithfully reflected by changes in binding activity. Estradiol caused receptor “processing” within 4 h of administration followed by recovery or “replenishment” of ER levels to the initial level by 20 h. The term “processing” has previously been used to describe the loss of ER binding activity in the early phase of estradiol-action, but it was never clear whether the ligand binding site was inactivated by processing or if the receptor molecule actually disappeared. This study shows that receptor “processing” constitutes disappearance of receptor protein and the later “replenishment” phase represents new ER protein rather than recycling of “processed” receptor. Progesterone-action, on the other hand, influenced only the “replenishment” phase by blocking recovery of ER protein. ER mRNA was suppressed by estradiol at 8 h, after the receptor was “processed” and “replenishment” already initiated. Progesterone, on the other hand, did not alter the steady state level of the message. Other mechanisms, such as regulation of translation rate of existing mRNA and changes in the rate of degradation of ER proteins are more likely involved in acute regulation of ER by these ovarian steroid hormones.     

Comparative Transcriptome Analyses Reveal Genes Related to Spine Development in Cucumber (<i>Cucumis sativus</i>)

Fruit spine is an important quality trait of cucumber. To better understand the molecular basis of cucumber spine development and function, RNA-Seq was performed to identify differentially expressed genes (DEGs) in fruit spines of different development stages, namely, 8 days before anthesis (SpBA8), anthesis (SpA) and 8 days after anthesis (SpAA8). Stage-wise comparisons obtained 2,259 (SpBA8 vs. SpA), 4,551 (SpA vs. SpAA8), and 5,290 (SpBA8 vs. SpAA8) DEGs. All the DEGs were classified into eight expression clusters by trend analysis. Among these DEGs, in addition to the Mict, Tril, CsTTG1, CsMYB6, NS, and Tu genes that have been reported to regulate fruit spine formation, we found that the CsHDG11, CsSCL8, CsSPL8, CsZFP6 and CsZFP8 may also be involved in spine development in cucumber. Our study provides a theoretical basis for further research on molecular mechanisms of spine development in cucumber.     

Melatonin Promotes Rice Seed Germination under Drought Stress by Regulating Antioxidant Capacity

Drought stress is a serious threat to the germination of plant seeds and the growth of seedlings. Melatonin has been proven to play an important role in alleviating plant stress. However, its effect on seed germination under drought conditions is still poorly understood. Therefore, we studied the effects of melatonin on rice seed germination and physiological characteristics under drought stress. Rice seeds were treated with different concentrations of melatonin (i.e., 0, 20, 100, and 500 μM) and drought stress was simulated with 5% polyethylene glycol 6000 (PEG6000). The results showed that 100 μM melatonin can effectively improve the germination potential, rate and index; the vigor index of rice seeds; and the length of the shoot and root. In addition, that treatment also increased the activity of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT), and reduced the content of malondialdehyde (MDA). The grey relational grade between the shoot MDA content and the melatonin seed-soaking treatment was the highest, which could be useful for evaluating the effect of melatonin on drought tolerance. Two-way analysis of variance showed that the effect of single melatonin treatment on rice seeds was more significant than that of single drought stress and interaction treatment of drought and melatonin (p < 0.05). The subordinate function results showed that 100 μM melatonin significantly improved the germination and physiological indexes of rice seeds and effectively alleviated the adverse effects of drought stress on rice seedlings. The results helped to improve the understanding of the morphological and physiological involvement of melatonin in promoting seed germination and seedling development under drought stress.     

ε-聚赖氨酸抑菌性能的研究进展

ε-聚赖氨酸(ε-poly-L-lysine,ε-PL)是抑菌谱广泛的天然抑菌剂,由通过α-羧基与ε-氨基连接的25–35个赖氨酸聚合而成。ε-PL主要由白色链霉菌发酵生产所得,比化学生产更加高效和环保。ε-PL具有水溶性好、耐热和对环境无污染等特点,具有良好的应用前景。本文从发酵生产入手,着重综述了ε-PL对各种微生物抑菌性能、抑菌机制及抑菌机制模型的研究进展。推测ε-PL是通过对细胞膜的破坏而改变细胞的通透性,或者作用到细胞内引起活性氧(reactive oxygen species, ROS)胁迫而影响调节基因的表达,从而起到抑菌作用。根据这2种抑菌方式分别建立了相应的抑菌模型,即毡毯模型和ROS诱导细胞凋亡模型。本文可为ε-PL对微生物抑制性能的深入研究提供依据,同时也提出了ε-PL抑菌机制的新模型,为扩展ε-PL应用领域提供了一定的参考。     

温州地区小杓鹬的代谢产热特征

动物能量代谢相关的生理生态特征与其地理分布密切相关。为探讨温州地区迁徙鸟类小杓鹬(Numenius minutus)的代谢产热特征及体温调节,本文在环境温度(T_a)5.0～42.5℃范围内,测定了小杓鹬的代谢率(R_m,以单位时间耗氧量表示,ml/h)和体温,并计算不同环境温度的热传导。结果显示：在环境温度为5～35℃的范围内,小杓鹬的体温维持相对恒定,平均体温为(42.8±0.10)℃;热中性区为27.5～40.0℃;在热中性区温度范围内,代谢率即基础代谢率为(221.31±6.01)ml/h,是体重预期值的141%;环境温度在5.0～27.5℃范围内,代谢率与环境温度(T_a,℃)呈负相关,回归方程为R_m=587.10﹣11.78 T_a;在5.0～27.5℃的环境温度范围内,小杓鹬的热传导最低,平均为(0.11±0.00)ml/(g·h·℃),是体重预期值的212%;代谢预期比和热传导预期比的比值(F值)为1.21,表明该物种有较好的体温调节能力。小杓鹬具有较高的体温和基础代谢...     

基因重组与外源铁离子对大肠杆菌合成血红素的影响

【背景】大肠杆菌通过C5途径合成卟啉及血红素,5-氨基乙酰丙酸(5-aminolevulinic acid,5-ALA)是C5途径中关键的前体物质,血红素由原卟啉IX (protoporphyrin IX, PPIX)螯合一个铁离子所形成,目前5-ALA与PPIX的外泌对卟啉的积累和血红素合成的影响尚不清楚。【目的】构建5-ALA外泌蛋白基因rhtA和卟啉外泌蛋白基因tolC双缺失的大肠杆菌以积累卟啉,同时外源添加铁离子,并过表达亚铁螯合酶基因hemH及参与铁摄取的基因efeB,促进卟啉向血红素的转化。【方法】通过Red同源重组敲除大肠杆菌BL21(DE3)的rhtA和tolC,并外源添加不同浓度的FeSO₄及Fe₂(SO₄)₃,同时构建重组质粒pEHE过表达hemH和efeB,检测卟啉和血红素含量,分析卟啉向血红素的转化。【结果】敲除rhtA和tolC对菌体生长无显著影响,与野生菌WT相比,敲除菌株WT-RT的卟啉含量增加,血红素合成略有提升。外源添加100μmol/L Fe²⁺     

基于微波热声层析成像定量重建生物组织电导率的改进方法

目的 生物电磁学参数中的电导率与组织的功能性信息直接相关,精准重建生物组织电导率在医学成像技术和医学诊断领域中有着重要意义。本文改进定量微波热声层析成像（microwave-induced thermoacoustic tomography,MTAT）算法,使组织电导率的重建精度提高。方法 本文在利用有限元离散法求解热声波动方程和亥姆霍兹方程的基础之上,提出了一种基于正则化牛顿迭代法（regularized Newton iteration method,RNIM）定量重建组织电导率的改进方法。结果 通过数值模拟实验和含不同浓度NaCl溶液的仿体实验,验证了算法改进的有效性。组织仿体实验结果表明,目标在不同位置、不同大小、不同对比度情况下,相比于定量微波热声层析成像采用拟合（fitting）的方法,采用正则化牛顿法定量重建的仿体电导率相对误差明显降低,重建目标精度提高。在仿体实验中采用RNIM方法重建相同浓度的单目标在不同位置的电导率变化幅度更小,以及重建多目标电导率的相对比值与实际更接近,实验结果验证了改进方法的稳定性。结论 研究结果表明优化算法能更加准确地定量重建组织仿体的电导率,...