Dexmedetomidine attenuates lipopolysaccharide-induced acute liver injury in rats by inhibiting caveolin-1 downstream signaling pathway

Objective: The aim of the present study is to investigate the anti-injury and anti-inflammatory effects of dexmedetomidine (Dex) in acute liver injury induced by lipopolysaccharide (LPS) in Sprague–Dawley rats and its possible mechanism.Methods: The acute liver injury model of male rats was established by injecting LPS into tail vein. The mean arterial pressure (MAP) of rats was recorded at 0–7 h, and lactic acid was detected at different time points. Wet/dry weight ratio (W/D) was calculated. Pathological changes of rat liver were observed by HE staining. ALT and AST levels in serum were detected. The activities of myeloperoxidase (MPO) and superoxide dismutase (SOD) in liver tissue homogenate and the levels of IL-1β and IL-18 in serum were detected by ELISA. Protein levels of Caveolin-1 (Cav-1), TLR-4 and NLRP3 in liver tissue were tested by immunohistochemistry method. The expression of Cav-1, TLR-4 and NLRP3 mRNA in liver tissue was detected by quantitative polymerase chain reaction (qPCR) to explore its related mechanism.Results: Compared with NS group, serum lactic acid, W/D of liver tissue, MPO, SOD, IL-1β and IL-18 were significantly increased and MAP decreased significantly in LPS group and D+L group. However, compared with NS group, D group showed no significant difference in various indicators. Compared with LPS group, MPO, SOD, IL-1β and IL-18 were significantly decreased and MAP was significantly increased in D+L group. D+L group could significantly increase the level of Cav-1 protein and decrease the level of TLR-4 and NLRP3 protein in liver tissue caused by sepsis. The expression of Cav-1 mRNA was significantly up-regulated and the expression of TLR-4 and NLRP3 mRNA was inhibited in D+L group.Conclusion: Dex pretreatment protects against LPS-induced actue liver injury via inhibiting the activation of the NLRP3 signaling pathway by up-regulating the expression of Cav-1 by sepsis.     

TOR-autophagy signaling in adult zebrafish models of cardiomyopathy

The target of rapamycin (TOR) kinase is part of an evolutionarily conserved signaling pathway that coordinates cell growth, survival, and autophagy. Previously, pharmacological studies using rapamycin have suggested a cardioprotective effect of TOR signaling inhibition on cardiomyopathy. We found that rapamycin exerts a conserved cardioprotective effect in two adult zebrafish models of cardiomyopathy of different etiology, and provided the first genetic evidence to support a long-term cardioprotective effect of TOR signaling inhibition. Moreover, we detected dynamic TOR-autophagy activities along different stages of cardiomyopathy. This needs to be considered when developing TOR-autophagy-based therapeutics for cardiomyopathy.     

Receptor-associated protein facilitates proper folding and maturation of the low-density lipoprotein receptor and its class 2 mutants

Familial hypercholesterolemia is the consequence of various mutations in the low-density lipoprotein receptor (LDLR). In the current study, we show that a specialized molecular chaperone, the receptor-associated protein (RAP), promotes proper folding and subsequent exocytic trafficking of the wild-type LDLR and several of its class 2 mutants. Co-immunoprecipitation with anti-RAP antibody demonstrates that RAP interacts with the LDLR. Kinetic analyses of LDLR posttranslational folding and maturation in the absence or presence of RAP coexpression show that RAP prevents aggregation and promotes the maturation of the LDLR. Additionally, depletion of Ca(2+) in intact cells impairs LDLR folding, and coexpression of RAP partially corrects this misfolding. Finally, we show that the increased mature cell surface LDLR in the presence of RAP coexpression is functional in its ability to endocytose and degrade (125)I-LDL. Taken together, our results show that the folding, trafficking, and maturation of the LDLR and its class 2 mutants are promoted by RAP.     

用亲和素-生物素复合物法研究流行性乙型脑炎病毒感染小鼠中枢神经系统后的抗原定位

利用亲和素-生物素免疫组织化学技术,研究了流行性乙型脑炎(简称乙脑)病毒抗原(P3,A2株)感染小鼠中枢神经系统后的定位。观察到乙脑病毒抗原分布具有一定选择性,主要集中在脑干、小脑、间脑和大脑皮质。病变分布与H-E常规病理染色一致。该方法敏感、特异。同时比较了兔免疫血清与乙脑单克隆抗体的应用效果。对组织化学冰冻切片漂浮法诊断病毒抗原进行了探讨。     

抗逆放线菌的多样性、功能特性及其在环境修复中的应用

放线菌(actinomycetes)是一类可生存于各种极端环境的特殊菌群,具备较强的抗逆特性。其种类丰富,功能多样,适应性强,已被广泛用于抗生素开发、生物防治和环境修复等领域。放线菌可调节土壤微生物群落结构、介导营养元素转化和植物吸收、催化有机污染物降解及重金属的氧化还原过程,该特性赋予其在土壤改良、地力维持和污染物去除等方面广阔的环境应用前景。本文综述了放线菌的多样性、环境分布以及放线菌对环境改良和污染物去除的特性与机制,结合在环境修复领域的应用现状,总结了放线菌修复技术的优势及发展方向。     

雉鸡的活动痕迹及种群密度的初步研究

本文报道了在不同生境中采用样方法对雉鸡及其活动痕迹进行调查,并根据Ｄ＝Ｎ／Ｂ公式对所得的数据加以处理,其结果表明雉鸡在活动过程中所留下的巢、粪便等痕迹均以灌草丛为最多,而取食刨土所留下的痕迹则以农耕地为最多。其种群密度,在草坡为５６只／ｋｍ２,稀树灌丛草坡为７８只／ｋｍ２,灌丛草坡为１５６只／ｋｍ２。     

长三角地区城市密度对碳排放绩效的影响效应与机制

城市密度是衡量城市各要素空间集聚程度的表征也是调控城市各要素资源分配效率的重要手段。过往主要围绕城市密度的物质形态测度来研究城市空间资源利用与环境问题,少有立足碳排放绩效的视角来研究城市密度的演变逻辑。立足生态效益中自然资源投入最小化与获得价值最大化的观点,从经济、社会、环境三个维度构建碳排放绩效综合评价指标,以长三角41个城市为例,基于标准差椭圆分析城市密度与碳排放绩效的时空演变及关联特征,采用地理加权回归模型与地理探测器相结合的方法,确定城市密度对碳排放绩效的影响效应及机制。结果表明:(1)城市密度与碳排放绩效均升高,城市密度增速减慢,而碳排放绩效增速加快;二者均呈东南-西北向发展且关联性不断增强。(2)城市密度分指标对碳排放绩效的影响效应存在时空差异,东南部多数城市各分指标影响系数增大且作用方向不变;西北部人口密度负向影响显著增强,经济密度的影响由负转正,而空间密度的影响由正转负。(3)城市密度与其他经济社会因素交互后对碳排放绩效产生影响,其中经济密度与产业结构协同作用对碳排放绩效的影响最大,且与因子独立作用相比,人口密度与其他影响因素的交互效应增幅最大。理清城市密度对碳排放绩效的影响效应及机制,可以为城市空间结构的合理优化提供依据。     

Protective effect of aldehyde dehydrogenase 2 against rat corneal dysfunction caused by streptozotocin-induced type I diabetes

Aldehyde dehydrogenase 2 plays a pivotal role in detoxifying aldehydes, and our previous study revealed that aldehyde dehydrogenase 2 could alleviate diabetic retinopathy-associated damage. We aimed to characterize the potential role of aldehyde dehydrogenase 2 in diabetic keratopathy. Twenty-four rats with streptozotocin-induced (60 mg/kg, single intraperitoneal injection) type 1 diabetes mellitus (T1DM) were divided the T1DM group and the T1DM + Alda1 (an activator of aldehyde dehydrogenase 2) group (5 mg/kg/d, intraperitoneal injection, 1/2/3 months), while an additional 12 healthy rats served as the control group. Corneal morphology was examined in vivo and in vitro at one, two, and three months after T1DM induction. Additionally, serum inflammatory factors were measured by ELISA, and the expression of corneal vascular endothelial growth factor A (VEGF-A) and aldehyde dehydrogenase 2 was measured by immunofluorescence staining. Corneal cell death was evaluated by terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining. Slit lamp analysis showed that the area of corneal epithelial cell injury in the T1DM + Alda1 group was significantly smaller than that in the T1DM group at one and two months after T1DM induction (all P < 0.05). OCT analysis and HE staining showed that the central corneal thickness (indication of corneal edema) and the epithelial keratinization level in the T1DM + Alda1 group was evidently decreased compared with those in the T1DM group (all P < 0.05). The serum inflammatory factors interleukin-1 and interleukin-6 were significantly upregulated in the T1DM group compared with the T1DM + Alda1 group at three months after T1DM induction (all P < 0.05), while there were no differences in SOD or TNF-α levels among all groups. Furthermore, corneal VEGF-A expression and corneal cell death in the T1DM + Alda1 group were dramatically reduced compared to those in the T1DM group (all P < 0.05). In conclusion, the aldehyde dehydrogenase 2 agonist Alda1 attenuated rat corneal dysfunction induced by T1DM by alleviating corneal edema, decreasing corneal cell death, and downregulating corneal VEGF-A expression.