Activation of the wnt/β-catenin/CYP1B1 pathway alleviates oxidative stress and protects the blood-brain barrier under cerebral ischemia/reperfusion conditions

Accumulating evidence suggests that oxidative stress and the Wnt/β-catenin pathway participate in stroke-induced disruption of the blood-brain barrier.However,the potential links between them following ischemic stroke remain largely unknown.The present study found that cerebral ischemia leads to oxidative stress and repression of the Wnt/β-catenin pathway.Meanwhile,Wnt/β-catenin pathway activation by the pharmacological inhibito r,TWS119,relieved oxidative stress,increased the levels of cytochrome P4501B1(CYP1B1)and tight junction-associated proteins(zonula occludens-1[ZO-1],occludin and claudin-5),as well as brain microvascular density in cerebral ischemia rats.Moreove r,rat brain microvascular endothelial cells that underwent oxygen glucose deprivation/reoxygenation displayed intense oxidative stress,suppression of the Wnt/β-catenin pathway,aggravated cell apoptosis,downregulated CYP1B1and tight junction protein levels,and inhibited cell prolife ration and migration.Overexpression ofβ-catenin or knockdown ofβ-catenin and CYP1B1 genes in rat brain mic rovascular endothelial cells at least partly ameliorated or exacerbated these effects,respectively.In addition,small interfering RNA-mediatedβ-catenin silencing decreased CYP1B1 expression,whereas CYP1B1 knoc kdown did not change the levels of glycogen synthase kinase 3β,Wnt-3a,andβ-catenin proteins in rat brain microvascular endothelial cells after oxygen glucose deprivatio n/reoxygenation.Thus,the data suggest that CYP1B1 can be regulated by Wnt/β-catenin signaling,and activation of the Wnt/β-catenin/CYP1B1 pathway contributes to alleviation of oxidative stress,increased tight junction levels,and protection of the blood-brain barrier against ischemia/hypoxia-induced injury.

Expanding catalytic promiscuity of a bifunctional terpene synthase through a single mutation-induced change in hydrogen-bond network within the catalytic pocket

Fungal bifunctional terpene synthases(BFTSs)catalyze the formation of numerous di-/sester-/tri-terpenes skeletons.However,the mechanism in controlling the cyclization pattern of terpene scaffolds is rarely deciphered for further application of tuning the catalytic promiscuity of terpene synthases for expanding the chemical space.In this study,we expanded the catalytic promiscuity of Fusarium oxysporum fusoxypene synthase(FoFS)by a single mutation at L89,leading to the production of three new sesterterpenes.Further computational analysis revealed that the reconstitution of the hydrogen-bond(H-bond)network of second-shell residues around the active site of FoFS influences the orientation of the aromatic residue W69 within the first-shell catalytic pocket.Thus,the dynamic orientation of W69 alters the carbocation transport,leading to the production of diverse ring system skeletons.These findings enhance our knowledge on understanding the molecular mechanisms,which could be applied on protein engineering terpene synthases on regulating the terpene skeletons.

Spatial patterns of urban green space and its actual utilization status in China based on big data analysis

Urban green space(UGS)is essential for sustainable urbanization and human well-being.The utilization status of UGS is closely related to the provision of ecosystem services for urban residents.Limitations on data availability,however,have led to the absence of a comprehensive approach for evaluating the actual utilization status of UGS at a large scale.Furthermore,differences in actual UGS utilization between intra-urban and peri-urban areas have not received enough attention.This study used big data analysis by combining point of interest(POI)and land use and cover change(LUCC)to quantify the spatial patterns of UGS utilization,and to evaluate the actual utilization status of UGS in 366 cities on the Chinese mainland.We also explored the differences in the actual utilization of UGS in intra-urban and peri-urban areas.The results showed that 94.01%of UGS resources in China had not been utilized.There was a clear pattern of spatial mismatch between the stock and the actual utilization of UGS,especially in the north-western region indicated by the Hu Huanyong Line.The actual utilization rate of UGS was closely related to the regional develop-ment level.There was a certain mismatch between the actual utilization and stock of intraurban green space(IUGS).The hot spots of the actual utilization rate of IUGS were in Yunnan,Guizhou,and Sichuan Provinces in southwestern China.The differ-ences in UGS actual utilization rates between IUGS and peri-urban green space(PUGS)were small in eastern China,but large in south-western and northwestern China.The actual utilization rate of IUGS in most Chinese cities was significantly larger than that of PUGS,indicating that PUGS were not well utilized.Our results provide scientific support for urban and regional planners in targeting specific areas for UGS design and development,and in optimizing future UGS planning in China.

高次谐波类共振增强的玻姆力学诠释

实验研究发现,高次谐波强度会随驱动光强度增大先急剧增强、而后减弱,这种对激光强度高度敏感的现象被称为高次谐波类共振增强.然而,人们对该现象的产生机制尚存在争议,其原因是现有物理解释所依赖的理论方法存在一些不足.玻姆力学是量子力学的一个版本,具有物理图像清晰、计算准确等特点,可以部分克服现有理论方法不足.本文利用玻姆力学研究高次谐波类共振增强,发现仅用一条玻姆轨道即可很好地重现高次谐波谱中的类共振增强结构.对该玻姆轨道的动力学分析表明,此增强结构来源于量子势引起的电子轨道奇异振荡行为.进一步结合电子波函数分析发现,此行为与强激光场中原子共振激发紧密相关.本研究深化了对高次谐波类共振增强现象的理解,有助于利用类共振增强提升谐波转化效率,获得高强度的阿秒光脉冲.

Greenspace’s value orientations of ecosystem service and socioeconomic service in China

Background:Natural ecosystems provide necessary services for human beings,including ecosystem service values(ESVs)and socioeconomic service values(SSVs).The value orientations of ESVs and SSVs are mainly related to people’s interaction with nature.This study reclassified greenspace from a perspective of exposed and non-exposed greenspace based on the level of interaction by people and greenspace.We applied an expert questionnaire to survey the SSVs value orientations of forestland,grassland,wetland,and water bodies,and quantitatively compared the value orientations between the ESVs and SSVs of greenspace in China.Result:(1)The values of exposed greenspace were relatively far higher than nonexposed greenspace,as it had both ESVs and SSVs.(2)The forestland and grassland had relatively high ESVs and SSVs,and are the priority for both the exposed and non-exposed greenspace.(3)Wetland had relatively high ESVs but low SSVs,which was unpopular for exposed greenspace.(4)The ESVs and SSVs of water body were relatively balanced.Conclusion:Greenspace had both ESVs and SSVs when they are exposed to human.Our study provided an innovative perspective to explore the value orientations of greenspace,which provides an actionable scientific basis for greenspace planning,design and construction in human habitat.