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。     

甜樱桃对高温胁迫的生理响应

为探讨甜樱桃对高温胁迫的响应机制,以1年生的甜樱桃嫁接盆栽苗为试材,研究了自然高温处理及胁迫后恢复对其叶片生理和超显微结构的影响。结果表明：经连续3d日最高气温均值达57.7℃胁迫后,甜樱桃叶片过氧化氢酶(CAT)和抗坏血酸过氧化物酶(APX)活性、超氧阴离子(O₂^·-)产生速率、非光化学淬灭系数(qN)显著增加,渗透调节物质可溶性蛋白、可溶性糖及脯氨酸含量显著提高,谷胱甘肽还原酶(GR)活性、叶绿素含量、PSII最大光化学效率(Fv/Fm)和电子传递速率(ETR)显著下降,超氧化物歧化酶(SOD)和过氧化物酶(POD)活性及光化学淬灭系数(qP)变化不显著。同时对叶片显超微结构观察发现,胁迫引起叶绿体变性,基质内囊体发生扭曲,部分基粒类囊体片层消失,出现大量巨型淀粉粒及嗜锇颗粒。恢复2d后SOD、POD、CAT、APX活性以及可溶性糖、可溶性蛋白、叶绿素总含量均显著下降,而GR活性和脯氨酸含量显著升高。以上表明,连续3d自然最高气温达57.7℃对甜樱桃叶片抗氧化系统和光合特性等产生了显著影响,叶绿体超显微结构受到明显破坏,对叶片造成了不可逆...     

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.     

番木瓜果糖-2,6-二磷酸酶CpF2KP基因克隆和蛋白表达纯化

番木瓜是岭南四大名果之一,在我国东南部地区广泛种植,因其具有食用和药用双重价值,因此深受人们的青睐。果糖-6-磷酸,2-激酶/果糖-2,6-二磷酸酯酶(fructose-6-phosphate,2-kinase/fructose-2,6-bisphosphatase,F2KP)是一个独特的双功能酶,具有激酶功能域和酯酶功能域,能催化生物体内糖代谢的重要调节物果糖-2,6-二磷酸(Fru-2,6-P_(2))的合成和降解。为了研究番木瓜中编码该酶的基因CpF2KP的功能,得到目的蛋白尤为重要。本研究从番木瓜基因组中提取到CpF2KP基因的编码序列(coding sequence,CDS)序列,该基因CDS全长2274 bp。将该基因CDS全长扩增之后选用pGEX-4T-1载体进行原核表达。对载体pGEX-4T-1用EcoRⅠ和BamHⅠ进行双酶切,利用基因重组的方式将扩增序列构建到原核表达载体上。经过诱导条件探索,SDS-PAGE结果显示GST-CpF2KP重组蛋白的大小约为110 kDa,诱导CpF2KP蛋白表达的最适条件为:异丙基β-D-硫代半乳糖苷(isopropyl beta-D-thiogalactopyranoside,IPTG)浓度为0.5 mmol/L,温度28℃。对诱导后的CpF2KP蛋白进行纯化,得到了纯化的单一目的蛋白。此外,检测了该基因的组织表达特性发现该基因在种子中表达量最高,在果肉中表达量最低。该研究为进一步深入揭示番木瓜CpF2KP蛋白的功能及研究该基因参与的生物学过程提供了重要基础。     

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...