Role of pulmonary epithelial arginase-II in activation of fibroblasts and lung inflammaging

Elevated arginases including type-I (Arg-I) and type-II isoenzyme (Arg-II) are reported to play a role in aging, age-associated organ inflammaging, and fibrosis. A role of arginase in pulmonary aging and underlying mechanisms are not explored. Our present study shows increased Arg-II levels in aging lung of female mice, which is detected in bronchial ciliated epithelium, club cells, alveolar type 2 (AT2) pneumocytes, and fibroblasts (but not vascular endothelial and smooth muscle cells). Similar cellular localization of Arg-II is also observed in human lung biopsies. The age-associated increase in lung fibrosis and inflammatory cytokines, including IL-1β and TGF-β1 that are highly expressed in bronchial epithelium, AT2 cells, and fibroblasts, are ameliorated in arg-ii deficient (arg-ii^−/−) mice. The effects of arg-ii^−/− on lung inflammaging are weaker in male as compared to female animals. Conditioned medium (CM) from human Arg-II-positive bronchial and alveolar epithelial cells, but not that from arg-ii^−/− cells, activates fibroblasts to produce various cytokines including TGF-β1 and collagen, which is abolished by IL-1β receptor antagonist or TGF-β type I receptor blocker. Conversely, TGF-β1 or IL-1β also increases Arg-II expression. In the mouse models, we confirmed the age-associated increase in IL-1β and TGF-β1 in epithelial cells and activation of fibroblasts, which is inhibited in arg-ii^−/− mice. Taken together, our study demonstrates a critical role of epithelial Arg-II in activation of pulmonary fibroblasts via paracrine release of IL-1β and TGF-β1, contributing to pulmonary inflammaging and fibrosis. The results provide a novel mechanistic insight in the role of Arg-II in pulmonary aging.     

一些海洋浮游植物量子产值的研究

现场实验以及用硅藻、金藻和绿藻所做的实验表明,在光饱和深度以下,随着深度的增加,浮游植物的量子产懂具有不变、增加和下降3种垂直变化趋势。偏离理论模式的后两种结果可能是由浮游植物的光强适应(Light-shade adaptation)等原因引起。还探讨了量子产值作为初级生产力模型和光利用效率模型中的参数的问题。     

气候变化导致青藏高原马鹿种群适应性分布退缩：以类乌齐马鹿国家级自然保护区为例

近50年青藏高原的气候变化速率是全球平均值的2倍,对高原有蹄类的种群分布和多样性维持带来严重影响。本研究以西藏类乌齐马鹿国家级自然保护区的马鹿种群为例,通过2013年和2021年对马鹿和牦牛种群数量、分布的调查,并整合了物种分布模型和种群动态模型,评估了当前和未来气候变化及人类活动(放牧、道路、居民点等)对马鹿种群适应性分布的影响。研究表明,马鹿种群在2013—2021年由890头增加到1 400头,根据种群增长模型预计在2050年马鹿种群数量将达到1 735头,但其适宜栖息地在2050年代下降43.4%,2070年代下降5.1%,表明马鹿种群增长与适宜栖息地缩小之间的冲突将不利于马鹿种群的可持续发展。同时,当前马鹿与牦牛栖息地重合率为19%,2050年代为60%,2070年代为37%,且牦牛与马鹿存在食物竞争,这在一定程度上减少了马鹿原有的适宜栖息地。为保护马鹿,建议减少牦牛的饲养量1 000～1 500头。本研究将种群增长模型、种间竞争关系与物种分布模型整合,把气候变化对物种的影响延伸到种群层面,对其他物种的保护具有借鉴意义。     

Thermostability enhancement of polyethylene terephthalate degrading PETase using self- and nonself-ligating protein scaffolding approaches

Polyethylene terephthalate (PET) hydrolase enzymes show promise for enzymatic PET degradation and green recycling of single-use PET vessels representing a major source of global pollution. Their full potential can be unlocked with enzyme engineering to render activities on recalcitrant PET substrates commensurate with cost-effective recycling at scale. Thermostability is a highly desirable property in industrial enzymes, often imparting increased robustness and significantly reducing quantities required. To date, most engineered PET hydrolases show improved thermostability over their parental enzymes. Here, we report engineered thermostable variants of Ideonella sakaiensis PET hydrolase enzyme (IsPETase) developed using two scaffolding strategies. The first employed SpyCatcher-SpyTag technology to covalently cyclize IsPETase, resulting in increased thermostability that was concomitant with reduced turnover of PET substrates compared to native IsPETase. The second approach using a GFP-nanobody fusion protein (vGFP) as a scaffold yielded a construct with a melting temperature of 80°C. This was further increased to 85°C when a thermostable PETase variant (FAST PETase) was scaffolded into vGFP, the highest reported so far for an engineered PET hydrolase derived from IsPETase. Thermostability enhancement using the vGFP scaffold did not compromise activity on PET compared to IsPETase. These contrasting results highlight potential topological and dynamic constraints imposed by scaffold choice as determinants of enzyme activity.     

葡萄蔗糖转化酶基因家族的生物信息学及响应逆境胁迫分析

蔗糖转化酶(invertase, INV)在植物生长发育和抵御胁迫中发挥着重要作用。研究从葡萄基因组数据库中鉴定出19个蔗糖转化酶基因,对基因结构和编码蛋白质的理化性质进行生物信息学分析,并利用qRT-PCR技术分析基因在不同激素和非生物胁迫条件下的表达特征,为进一步探索葡萄INV基因家族参与葡萄逆境响应提供了一定的理论依据。结果表明,(1)该基因家族编码蛋白的氨基酸长度在150～766 aa之间,理论等电点介于4.43～9.1之间,亚细胞定位预测发现其主要在细胞质中表达,此外液泡和细胞壁也存在部分基因表达;(2)共线性结果显示VvCINV与其他5个物种复制频率较高;(3)保守基序分析表明VvCwINV包含了所有的保守基序,且Glyco＿32和Glyco＿hydro＿100是VvINV基因主要结构域;(4)组织特异性表达分析发现多数基因在葡萄生长发育进程中都有表达;(5)qRT-PCR分析结果显示,VvINV基因家族在叶片中对激素处理和非生物胁迫的响应出现上调,VvCINV1在50 mg/L GA₃和10%PEG处理后上调表达极显著,VvCINV4在盐胁迫、ABA...     

相关遗传力抽样方差的估计

本文给出了单因子组和系统模型下有关相关传力及相关环境力抽样方差的估计方法。有关该参数在育种中的潜在应用其它与遗传相关之产间的相互关系也给予了一定的讨论。概括地来讲,相关遗传力具有遗传力和遗传相关的双重特征。遗传力是相关遗传力的一个特例而相关遗传力则是遗传力概念本身的扩展。用相关遗传力来表达性状间的相关遗传变异要比通常所用的遗传相关更准确一些。     

The Ethanol Extract of Syringa oblata Heartwood,a Mongolian Folk Medicine Containing Major Lignans,Exerts Analgesic and Sedative Effects on Mice

The heartwood of Syringa oblata Lindl. (SO) is one of Mongolian folk medicines to treat insomnia and pain, while its pharmacological evaluation and underlying mechanism remain unclear. In this study, the sedative effect of ethanol extract of SO (ESO) was evaluated with the locomotor activity test and the threshold dose of pentobarbital sodium-induced sleep test in mice, and the hot plate test, acetic acid-induced writhing test, and formalin test in mice were used to evaluate its analgesic effect. The underlying mechanism of ESO analgesia was explored by RT-PCR and western blot analysis, which is associated with the regulation of the NF-κB signaling pathway. Besides, the main constituents of ESO were characterized by LC/MS data analysis and comparison with isolated pure compounds. The current findings brought evidence for clinical application and further pharmacological and phytochemical studies on SO.     

Picroside III,an Active Ingredient of Picrorhiza scrophulariiflora,Ameliorates Experimental Colitis by Protecting Intestinal Barrier Integrity

This study aims to explore the protective effects of Picroside III, an active ingredient of Picrorhiza scrophulariiflora, on the intestinal epithelial barrier in tumor necrosis factor-α (TNF-α) induced Caco-2 cells and dextran sulfate sodium (DSS) induced colitis in mice. Results show that Picroside III significantly alleviated clinical signs of colitis including body weight loss, disease activity index increase, colon shortening, and colon tissue damage. It also increased claudin-3, ZO-1 and occludin expressions and decreased claudin-2 expression in the colon tissues of mice with colitis. In vitro, Picroside III also significantly promoted wound healing, decreased the permeability of cell monolayer, upregulated the expressions of claudin-3, ZO-1 and occludin and downregulated the expression of claudin-2 in TNF-α treated Caco-2 cells. Mechanism studies show that Picroside III significantly promoted AMP-activated protein kinase (AMPK) phosphorylation in vitro and in vivo, and blockade with AMPK could significantly attenuate the upregulation of Picroside III in ZO-1 and occludin expressions and the downregulation of claudin-2 expression in TNF-α treated Caco-2 cells. In conclusion, this study demonstrates that Picroside III attenuated DSS-induced colitis by promoting colonic mucosal wound healing and epithelial barrier function recovery via the activation of AMPK.