Human serum-derived exosomes modulate macrophage inflammation to promote VCAM1-mediated angiogenesis and bone regeneration

During exogenous bone-graft-mediated bone defect repair, macrophage inflammation dictates angiogenesis and bone regeneration. Exosomes from different human cells have shown macrophage immunomodulation-mediated bone regeneration potential. However, the effect of human serum-derived exosomes (serum-Exo) on macrophage immunomodulation-mediated angiogenesis during bone defect repair has not been investigated yet. In this study, we explored the effects of serum-Exo on macrophage inflammation regulation-mediated angiogenesis during bone defect repair and preliminarily elucidated the mechanism. Healthy serum-Exo was isolated by ultracentrifugation. The effect of serum-Exo on LPS-induced M1 macrophage inflammation was analysed in vitro. The conditioned medium of serum-Exo-treated LPS-induced M1 macrophage (serum-Exo-treated M1 macrophage-CM) was used to culture human umbilical vein endothelial cells (HUVEC), and the effect on angiogenesis was analysed by western blot, qRT-PCR, etc. mRNA-sequencing of HUVECs was performed to identify deferentially expressed genes. Finally, the rat mandibular defect model was established and treated with Bio-Oss and Bio-Oss + Exo. The effect of the Bio-Oss + Exo combination on mandibular bone regeneration was observed by micro-computed tomography (micro-CT), haematoxylin and eosin (HE) staining, Masson staining, and immunohistochemical staining. Serum-Exo promoted the proliferation of RAW264.7 macrophages and reduced the expression of M1-related genes such as IL-6, IL-1β, iNOS, and CD86. Serum-Exo-treated M1 macrophage-CM induced the proliferation, migration, and angiogenic differentiation of HUVEC, as well as the expression of H-type blood vessel markers CD31 and endomucin (EMCN), compared with M1 macrophage-CM. Moreover, higher expression of vascular endothelial adhesion factor 1 (VCAM1) in HUVEC cultured with serum-Exo-treated M1 macrophage-CM compared with M1 macrophages-CM. Inhibition of VCAM1 signalling abrogated the pro-angiogenic effect of serum-Exo-treated M1 macrophage-CM on HUVEC. Local administration of serum-Exo during mandibular bone defect repair reduced the number of M1 macrophages and promoted angiogenesis and osteogenesis. Collectively, our results demonstrate the macrophage inflammation regulation-mediated pro-angiogenic potential of serum-Exo during bone defect repair possibly via upregulation of VCAM1 signalling in HUVEC.     

印度查谟地区甜橙上柑桔潜叶蛾为害动态及其与重要气候因子的关系(英文)

本研究旨在揭示印度查谟柑桔潜叶蛾Phyllocnistis citrella Stainton为害甜橙Citrus sinensis的季节性变化,以及降雨量、相对湿度和温度等重要的气候因子对其种群的影响。本文对不同季节印度查谟的一个甜橙园里的柑桔潜叶蛾丰度进行了调查, 从2005年3月到2008年2月每两周调查一次。柑桔潜叶蛾在一年内有3个为害高峰,分别是4月中旬、7月中旬和9月中旬,这与甜橙新营养梢的生长期相吻合。相关分析表明,上午和下午的相对湿度和平均相对湿度与柑桔潜叶蛾的数量呈负相关;然而,平均降雨量、最高气温、最低气温和平均气温与柑桔潜叶蛾的数量呈正相关。降雨量和温度与柑桔潜叶蛾为害程度呈显著正相关。总之,柑桔潜叶蛾的数量不能简单地通过观察某一特殊地区的相对湿度来预测,而降雨量和温度在影响虫害方面均起着重要的作用。     

Cholesterol biosensors based on oxygen sensing alginate-silica microspheres

Cholesterol determination in body is important in diagnosis of diseases like coronary heart disease, arteriosclerosis, diabetes, and obstructive jaundice. This research aims at developing fluorimetric cholesterol biosensors based on self-assembled mesoporous alginate-silica (Algilica) microspheres. For preparing the biosensor, Pt-(II)-octaethylporphine (PtOEP; oxygen sensitive metalloporphyrin) dye has been loaded in the Algilica microspheres using the solvent-mediated precipitation method. Cholesterol oxidase (ChOx) was then covalently conjugated to PtOEP/Algilica microspheres using EDC and NHS reagents. PtOEP dye and enzyme encapsulation, activity and stability were then analyzed. Layer-by-layer self-assembly was finally performed using PAH and PSS polyelectrolytes to minimize leaching of the biosensor components. The prepared biosensor exhibited linearity over a range of 0.77-2.5 mM O(2) (K(SV) : 0.097/mM of O(2) ) obtained using from Stern-Volmer plots. The biosensor response to standard cholesterol displayed a linear analytical range from 1.25 to 10 mM of cholesterol with regression coefficient of 0.996 (1.25-3.75 mM), 0.976 (1.25-6 mM), and 0.959 (1.25-10 mM) and response time of 10 min. Thus, the prepared cholesterol biosensor shows great potential in the diagnosis of hypercholesterolemia.