Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism

Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.

Highly Efficient Broadband Achromatic Microlens Design Based on Low-Dispersion Materials

Metalenses with achromatic performance offer a new opportunity for high-quality imaging with an ultracompact configuration;however,they suffer from complex fabrication processes and low focusing efficiency.In this study,we propose an efficient design method for achromatic microlenses on a wavelength scale using materials with low dispersion,an adequately designed convex surface,and a thickness profile distribution.By taking into account the absolute chromatic aberration,relative focal length shift(FLS),and numerical aperture(NA),microlens with a certain focal length can be realized through our realized map of geometric features.Accordingly,the designed achromatic microlenses with low-dispersion fused silica were fabricated using a focused ion beam,and precise surface profiles were obtained.The fabricated microlenses exhibited a high average focusing efficiency of 65%at visible wavelengths of 410-680 nm and excellent achromatic capability via white light imaging.Moreover,the design exhibited the advantages of being polarization-insensitive and near-diffraction-limited.These results demonstrate the effectiveness of our proposed achromatic microlens design approach,which expands the prospects of miniaturized optics such as virtual and augmented reality,ultracompact microscopes,and biological endoscopy.

Expression of neurocan mRNA and ultrastructure of brain tissue after cerebral ischemia and reperfusion in stroke-prone renovascular hypertensive rats treated by electroacupuncture

We established a stroke-prone renovascular hypertensive rat model by bilateral constriction of the renal artery with sliver loop clips. After ten weeks, middle cerebral artery occlusion was induced for 2 hours. The rats then received electro-acupuncture at Baihui （DU 20） and Dazhui （DU 14） after onset of ischemia for 30 days. In situ hybridization study showed that electroacupuncture significantly reduced the number of neurocan mRNA-positive cells in the ischemic penumbra and hippocampal tissues of rats. Electron microscopy results demonstrated that the structure of neurons and blood vessels in the ischemic tissues were restored with electroacupuncture. Overall, these data suggest that electroacupuncture may protect neurons against ischemic reperfusion injury in stroke-prone renovascular hypertensive rats, which may be regulated by downregulation of expression of nerve inhibitory factor neurocan mRNA.

Neuroprotective effect of the traditional Chinese herbal formula Tongxinluo: a PET imaging study in rats

Tongxinluo has been widely used in China for the treatment of acute stroke and for neuroprotection. However, there are few positron emission tomography （PET） studies on the neuroprotective effect of Tongxinluo on cerebral ischemia/reperfusion in small animals. In the present study, Tongxinluo superfine powder suspension or its vehicle was administered intragastrically to rats for 5 successive days before middle cerebral artery occlusion, ^18Ffluorodeoxyglucose （FDG） small animal PET imaging showed that at 1 and 2 weeks after cerebral ischemia/reperfusion, glucose metabolism in the ischemic area was greater in rats that had received Tongxinluo than in those that had received the vehicle. Nissl staining showed that 2 weeks after cerebral ischemia/reperfusion, there was less neuronal loss in the prefrontal cortex in Tongxinluo-treated rats than in controls. In addition, Tongxinluo-treated animals showed better neurologic function and lower cerebral infarct volume than rats that received the vehicle. These findings suggest that Tongxinluo exhibits neuroprotective effects in cerebral ischemia/reperfusion injury and demonstrates that ^18F-FDG small animal PET imaging is a useful tool with which to study the molecular pharmacology of traditional Chinese medicine.

Metamaterials:From Engineered Materials to Engineering Materials

As a new frontier in materials science,metamaterials have experienced a boom in the past two decades.This research field began with artificially structured materials exhibiting extraordinary electromagnetic properties unavailable in nature;now,it extends to a large family of artificial-material systems with wide-ranging,extraordinary,and outstanding properties for applications in fields such as electromagnetics,optics,mechanics.

Effect of cyclovirobuxine D on human growth-associated protein 43 and neurocan expression in ischemic brain tissue of stroke-prone renovascular hypertensive rats

BACKGROUND： Experimental data indicate that human growth-associated protein 43 mRNA expression coincides with axonal growth during nerve ganglion development; while neurocan, secreted from astrocytes, can inhibit sprouting and elongation of the axonal growth cone. OBJECTIVE： To verify regulatory effects of cyclovirobuxine D （CVB-D） extracted from Chinese box branchlet on human growth-associated protein 43 （GAP-43）, and neurocan expression in brain tissue of stroke-prone renovascular hypertensive （RHRSP） rats, at different time points after cerebral ischemia/reperfusion. DESIGN： Randomized grouping design and controlled animal study. SETTING： This study was performed at the Center of Guangdong Hospital of Traditional Chinese Medicine （a national key laboratory） from March 2003 to September 2006. MATERIALS： 100 healthy male Sprague-Dawley rats, aged 2 3 months and weighing 90-120 g, were selected for this study. CVB-D was provided by Nanjing Xiaoying Pharmaceutical Factory （Batch number： 307701）. METHODS： The initial tip of renal arteries was clamped bilaterally for 10 weeks to establish the RHRSP model. 100 RHRSP rats were randomly divided into 4 groups： naive group （n = 10）, sham surgery group （n = 10）, CVB-D group （n = 40）, and lesion group （n = 40）. Rats in the naive group did not undergo any treatment, and cervical vessels of rats in the sham surgery group were exposed, but not blocked. The right middle cerebral artery of rats in the CVB-D group and lesion group were occluded to establish cerebral ischemia. Rats in the CVB-D group were intraperitoneally injected with CVB-D （6.48 mg/kg） every day and with saline （1.5 mL/injection） twice a day. Rats in the lesion group were intraperitoneally injected with saline （2 mL/injection）. MAIN OUTCOME MEASURES： Immunohistochemistry was applied to detect GAP-43 and neurocan expression in the ischemic penumbra region of CVB-D and lesion brains at 2 hours post-cerebral ischemia and at 1, 7, 14, and 30 days post-perfusion （n = 10 at each time point）. Similarly, GAP-43 and neurocan expression was detected in the right hemisphere of naive and sham-operated animals. The results were expressed as positive cells. RESULTS： A total of 100 rats were included in the final analysis. The number of GAP-43 positive cells increased in the CVB-D group 1, 7, 14, and 30 days post-cerebral ischemia/perfusion compared to the lesion group, as indicated by a significant difference between the CVB-D and lesion group （P 〈 0.054）.01）. The number of neurocan-positive cells decreased in the CVB-D group on the first day compared to the model group; however, there was no significant difference between the two groups （P 〉 0.05）. On post-ischemia days 7, 14, and 30, the number of neurocan-positive cells in the CVB-D group was significantly less than in the lesion group （P 〈 0.05）. Both, GAP-43 and neurocan expression was not detectable in brains of naive and sham-operated animals. CONCLUSION： CVB-D treatment up-regulated GAP-43 expression and down-regulated neurocan expression in the ischemic region of RHRSP rats.

Study on the Correlation between Teaching Effectiveness and Task-based Teaching Method in College English Listening and Speaking

Teaching effectiveness has been discussed widely both in the theoretical studies and the practical teaching contexts. Teachingeffectiveness as a general teaching concept should be manifested based on a practical method. This study begins with the analysesof the effectiveness of English listening and speaking class and the task-based teaching method. It focuses on probing the positivecorrelation between teaching effectiveness and task-based teaching model in College English listening and speaking class. Throughanalyzing and comparing the important indicators of teaching effectiveness and task-based teaching model, the favorablecorrelation between the two can be verified. In conclusion, a few important factors of designing and conducting tasks in Englishlistening and speaking class are highlighted in order to substantially guarantee and enhance teaching effectiveness.

New Changes in Business English Teaching System under the Background of Big Data

Big data,as an advanced form of information technology,not only brings challenges for business conductions,which is greatly influencing people’s live,but also triggers changes in business English education.This paper,inspired by the rapid development of big data technology,attempts to probe the relationship between business English teaching and big data,the influences of big data technology on business English teaching innovation.The changes in business teaching theories,notions,models and environment created by big data will be specifically discussed and analyzed in this paper in order to facilitate teachers to better carry out teaching innovations.

商务英语专业应用型人才培养模式改革与实践-以北京物资学院商务英语专业为例

为提升商务英语专业人才应用能力,地方性本科院校商务英语专业建设过程中应注重人才培养模式的内涵与特色,保证课程体系的设置能够支持人才培养目标,要建立有效的课程教学与学习效果的评价体系,以确保培养的商务英语专业人才能够满足区域经济发展需求。

High‑permittivity ceramics enabled highly homogeneous zero‑index metamaterials for high‑directivity antennas and beyond

Zero-index metamaterials(ZIMs)can support uniform electromagnetic field distributions at any frequency,but their applications are hampered by the ZIM’s homogenization level—only 3 unit cells per free-space wavelength,which is fundamentally limited by the low-permittivity inclusions(εr≈12)and background matrix(εr≈1).Here,by filling high-permittivity SrTiO3 ceramic(εr≈294)pillars in BaTiO3(εr≈25)background matrix,we demonstrate a highly homogeneous microwave ZIM with an over threefold increase in the homogenization level.Leveraging such a ZIM,we achieve not only an antenna,approaching the fundamental limit in the directivity with outstanding scalability,but also a concave lens with a focal length of as short as 1λ0.Our highly homogeneous ZIM has profound implications in ceramics,ZIM-based waveguides and cavities,free-space wavefront manipulation,and microwave quantum optics,and opens up enormous possibilities in wireless communications,remote sensing,global positioning satellites,etc.

二芳基乙烯类酸致变色材料的光机械效应

本文合成了氟代萘乙烯基苯并唑BO1N4F和氟代萘乙烯基苯并噻唑BT1N4F,二者在紫外光照下可发生拓扑[2+2]环加成反应,生成的主产物为β-型二聚体.由于前者的光化学反应效率高于后者,因此,BO1N4F的光二聚反应导致晶体内部产生较大的张力.当累积在棒状晶体中的张力快速释放时,晶体发生爆裂,产生的碎片跳离原位置;当累积在针状晶体中的张力缓慢释放时,晶体发生显著的背光弯曲.此外,光二聚反应将平面形二芳基乙烯分子转化为蝴蝶形环丁烷衍生物,共轭分子的去平面化导致基于二聚体D-BO1N4F的薄膜对三氟乙酸蒸气的检测限低于薄膜BO1N4F.可见,光诱导[2+2]环加成反应不仅能改善二芳基乙烯衍生物在薄膜中的荧光传感性能,而且是分子晶体产生光机械效应的驱动力.

Zircon U-Pb Ages and Tectonic Implications of Late Paleozoic Volcanic Rocks in the Western Tianshan,North Xinjiang,China

The Late Paleozoic volcanic rocks are widespread in the Western Tianshan,and mainly consist of basalt,trachyte,trachy-andesite,andesite and rhyolite.However,the formation timing and tectonic implications of the volcanic rocks remain controversial.To obtain a comprehensive dataset with adequate spatial coverage,we collected the published zircon U-Pb age data of the Late Paleozoic volcanic rocks in the Western Tianshan,and mapped the temporal and spatial distribution of these volcanic rocks.Our compiled dataset indicates that the volcanic rocks in the Western Tianshan were formed in two major stages:Late Silurian-Early Carboniferous and Late Carboniferous-Middle Permian.The southward subduction of the Northern Tianshan Ocean formed a large number of Late Silurian-Early Carboniferous volcanic rocks.The flare-up of Late Carboniferous to Middle Permian magmatism in the NTOB was considered to be the response of the slab-roll back of the northern Tianshan Ocean.Therefore,arc magma assemblage and spatial-temporal distribution are of great significance to identify the dynamic mechanism transformation of subduction zone.

Late Mesozoic Tectono-Thermal History in the South Margin of Great Xing’an Range,NE China:Insights from Zircon and Apatite(U-Th)/He Ages

The Late Mesozoic tectono-thermal evolution and geodynamic setting of the Great Xing’an Range(GXR),particularly in the south margin,are still ambiguous.In this study,we present original low-temperature thermochronological data of six granitoid samples collected from Maanzi pluton in the south margin of the GXR.The apatite and zircon(U-Th)/He ages vary of 70.8 ± 4.3-119.0 ±7.0 Ma and 120.0 ± 7.1-146.7 ± 8.7 Ma,respectively.Further numerical inverse modeling results reveal that the granitoid plutons experienced a rapid cooling and exhumation stage during Early Cretaceous with a rate of ~5.0-6.0 ℃/Ma and ~0.14-0.17 mm/yr,respectively,including the western minor pluton emplaced during Early Permian and the major pluton crystallized in latest Jurassic,corresponding to the extensional tectonics in NE China.The rapid exhumation processes in the south margin of the GXR during the Early Cretaceous could be related to both the rollback of Paleo-Pacific oceanic plate and the collapse of thickened crust in the Mongol-Okhotsk Orogen.

Diffusion of helium in FCT zircon

To gain a better quantitative understanding of zircon(U-Th)/He ages and evaluate the applicability of zircon(U-Th)/He dating, the diffusion characteristics, He diffusion kinetics, helium partial retention zone(HePRZ), closure temperature, and(U-Th)/He ages were investigated using high-precision laboratory step heating experiments based on the thermally activated diffusion process. The ln(D/a^2) in Fish Canyon Tuff(FCT) zircons determined from laboratory step heating experiments was negatively correlated with reciprocal temperature, as expected for thermally activated volume diffusion. The zircon activation energies ranged from 144 to 184 kJ mol^(-1) with a mean of 169±12 kJ mol^(-1). The closure temperatures ranged from 144 to 216°C(a cooling rate of 10°C Ma^(-1) and an effective grain radius of 38–60 μm) with an average of 176±18°C. The calculated closure temperature increased with increasing cooling rate, yielding an average zircon He closure temperature of ～136°C at a slow cooling rate of 0.1°C Ma^(-1), whereas the closure value was ～199°C at a cooling rate of 100°C Ma^(-1). The closure temperature increased with the equivalent spherical radius assuming a constant cooling rate. The He ages from FCT zircons were negligibly affected by grain size because of the rapid cooling. He preserved in the zircon was sensitive to temperature and holding time, and the temperature range for zircon HePRZ gradually decreased with increasing holding time. The(U-Th)/He ages from 26 FCT zircons yielded an algorithmic mean of 28.3±0.3 Ma(S.E.) and a geometric mean of 28.4±0.3 Ma(S.E.), consistent with the ages of 28.4±1.9 Ma reported by other laboratories. The FCT zircons were characterized by rapid cooling, young(U-Th)/He ages with good reproducibility, and low alpha doses. Weak correlations between the He ages and effective uranium(eU) concentrations from the FCT zircons indicated radiation damage did not significantly affect He diffusivity.

Positive/Negative Phototropism:Controllable Molecular Actuators with Different Bending Behavior

Herein,a series of molecular actuators based on the crystals of(E)-2-(4-fluorostyryl)benzo[d]oxazole(BOAF4),(E)-2-(2,4-difluorostyryl)benzo[d]oxazole(BOAF24),(E)-2-(4-fluorostyryl)benzo[d]thiazole(BTAF4),and(E)-2-(2,4-difluorostyryl)benzo[d]thiazole(BTAF24)showed unique bending behavior under UV irradiation.The one-dimensional(1D)crystals of BOAF4 and BTAF4 bent toward light,whereas those of BOAF24 and BTAF24 bent away from light.Although the chemical structures of these compounds are similar,the authors found that F···H–C interaction played a key role in the different molecular packing in structures crystals,which led to the positive/negative phototropism of the actuators.Moreover,theoretical calculations were carried out to reveal the mechanical properties of the crystals.Taking advantage of these photomechanical properties,the authors achieved the potential application in pushing objects,as well as enriching and removing pollutants.Hence,the molecular actuators with different bending behavior could be fabricated by introducing different number of F atom,which may open a novel gate for crystal engineering.

Clathrin light chains regulate hypocotyl elongation by affecting the polarization of the auxin transporter PIN3 in Arabidopsis

PIN-FORMED(PIN)-dependent directional auxin transport is crucial for plant development. Although the redistribution of auxin mediated by the polarization of PIN3 plays key roles in modulating hypocotyl cell expansion, how PIN3 becomes repolarized to the proper sites within hypocotyl cells is poorly understood. We previously generated the clathrin light chain clc2-1 clc3-1 double mutant in Arabidopsis thaliana and found that it has an elongated hypocotyl phenotype compared to the wild type. Here, we performed genetic, cell biology, and pharmacological analyses combined with live-cell imaging to elucidate the molecular mechanism underlying the role of clathrin light chains in hypocotyl elongation. Our analyses indicated that the defects of the double mutant enhanced auxin maxima in epidermal cells, thus, promoting hypocotyl elongation. PIN3 relocated to the lateral sides of hypocotyl endodermal cells in clc2-1 clc3-1 mutants to redirect auxin toward the epidermal cell layers.Moreover, the loss of function of PIN3 largely suppressed the long hypocotyl phenotype of the clc2-1 clc3-1 double mutant, as did treatment with auxin transport inhibitors. Based on these data, we propose that clathrin modulates PIN3 abundance and polarity to direct auxin flux and inhibit cell elongation in the hypocotyl, providing novel insights into the regulation of hypocotyl elongation.