Insolubility of Cr2O3 in Bioaccessibility Tests Points to Requirement for a New Human Oral Reference Dose for Trivalent Chromium

Bioaccessibility measurements have the potential to improve the accuracy of risk assessments and reduce the potential costs of remediation when they reveal that the solubility of chemicals in a matrix (e.g., soil) differs markedly from that in the critical toxicity study (i.e., the key study from which a toxicological or toxicity reference value is derived). We aimed to apply this approach to a brownfield site contaminated with chromium, and found that the speciation was Cr^III, using a combination of alkaline digestion/diphenylcarbazide complexation and X-ray absorption near edge structure analysis. The bioaccessibility of Cr₂O₃, the compound on which a reference dose for Cr^III is based, was substantially lower (<0.1%) than that of the Cr^III in the soils, which was a maximum of 9%, giving relative bioaccessibility values of 13,000% in soil. This shows that the reference dose is based on essentially an insoluble compound, and thus we suggest that other compounds be considered for toxicity testing and derivation of reference dose. Two possibilities are CrCl₃·6H₂O and KCr(SO₄)₂·12H₂O, which have been used for derivation of ecological toxicity reference values and are soluble at a range of dosing levels in our bioaccessibility tests.     

Functional analysis of a miRNA‐like small RNA derived from Bombyx mori cytoplasmic polyhedrosis virus

Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) is a major pathogen of the economic insect silkworm, Bombyx mori. Virus‐encoded microRNAs (miRNAs) have been proven to play important roles in host–pathogen interactions. In this study we identified a BmCPV‐derived miRNA‐like 21 nt small RNA, BmCPV‐miR‐1, from the small RNA deep sequencing of BmCPV‐infected silkworm larvae by stem‐loop quantitative real‐time PCR (qPCR) and investigated its functions with qPCR and lentiviral expression systems. Bombyx mori inhibitor of apoptosis protein (BmIAP) gene was predicted by both target prediction software miRanda and Targetscan to be one of its target genes with a binding site for BmCPV‐miR‐1 at the 5′ untranslated region. It was found that the expression of BmCPV‐miR‐1 and its target gene BmIAP were both up‐regulated in BmCPV‐infected larvae. At the same time, it was confirmed that BmCPV‐miR‐1 could up‐regulate the expression of BmIAP gene in HEK293T cells with lentiviral expression systems and in BmN cells by transfecting mimics. Furthermore, BmCPV‐miR‐1 mimics could up‐regulate the expression level of BmIAP gene in midgut and fat body in the silkworm. In the midgut of BmCPV‐infected larvae, BmCPV‐miR‐1 mimics could be further up‐regulated and inhibitors could lower the virus‐mediated expression of BmIAP gene. With the viral genomic RNA segments S1 and S10 as indicators, BmCPV‐miR‐1 mimics could up‐regulate and inhibitors down‐regulate their replication in the infected silkworm. These results implied that BmCPV‐miR‐1 could inhibit cell apoptosis in the infected silkworm through up‐regulating BmIAP expression, providing the virus with a better cell circumstance for its replication.     

Synthesis and bioevaluation of new tacrine-cinnamic acid hybrids as cholinesterase inhibitors against Alzheimer’s disease

Small molecule cholinesterases inhibitor (ChEI) provides an effective therapeutic strategy to treat Alzheimer’s disease (AD). Currently, the discovery of new ChEI with multi-target effect is still of great importance. Herein, we report the synthesis, structure–activity relationship study and biological evaluation of a series of tacrine-cinnamic acid hybrids as new ChEIs. All target compounds are evaluated for their in vitro cholinesterase inhibitory activities. The representatives which show potent activity on cholinesterase, are evaluated for the amyloid β-protein self-aggregation inhibition and in vivo assays. The optimal compound 19, 27, and 30 (human AChE IC₅₀?=?10.2?±?1.2, 16.5?±?1.7, and 15.3?±?1.8?nM, respectively) show good performance in ameliorating the scopolamine-induced cognition impairment and preliminary safety in hepatotoxicity evaluation. These compounds deserve further evaluation for the development of new therapeutic agents against AD.     

县域城镇空间形态与居住建筑能耗关联性的连续尺度研究——以浙江长兴、福建连江为例

居住建筑能耗受建筑周边空间形态的直接影响，确定空间形态低碳效应及其最佳尺度将有助于实现县域城镇低碳转型。以浙江省长兴县、福建省连江县为例，共计选取49个具有代表性的居住建筑样本，采用GIS分析与数理统计相结合的方式，在居住建筑1800m半径范围内，以200m为间隔建立缓冲区，开展全年、最冷月份能耗期及最热月份能耗期建筑能耗与周边空间形态关联性的连续尺度研究。结果表明：(1)道路密度、开发密度、容积率均与建筑能耗呈正相关，但各指标对应的能耗时期、尺度范围有较大差异。(2)水面率、土地利用混合度是与建筑能耗相关的共性指标，但在不同地区的正负效应及尺度范围不同；(3)影响浙闽地区县域城镇最热月份能耗期能耗的关键形态因子为1000m-道路密度、800m-水面率、1600m-开放空间率；影响连江最冷月份能耗期能耗的关键形态因子为800m-水面率。(4)就控碳单元设置而言，长兴县可重点关注1000—1200m半径范围，连江县可重点关注800—1000m、1400m半径范围。(5)浙闽地区县域城镇特性指标为开放空间率，与最热月份能耗期建筑能呈负相关；长兴县特性指标为容积率、水岸密度，分别与全年、最冷...     

退化高寒草甸关键生态属性对多途径恢复措施的响应特征

高寒草甸是青藏高原的主体植被类型，但退化态势较为严峻，严重威胁青藏高原生态屏障的战略地位。退化高寒草甸的复健是世界性难题，治理效果也因退化状态、恢复措施及气候环境而异。以春季休牧、秋季休牧、畜群结构优化、减畜轮牧、围栏封育及翻耕改建等典型多途径恢复措施下的退化高寒草甸为对象，系统探讨主要生态要素和生态功能的响应特征及潜在过程。结果表明，典型恢复措施下退化高寒草甸的植被生产力、土壤有机碳密度及土壤饱和持水量等生态要素都得到一定程度的提升，而恢复效果与实施年限及恢复措施密切相关。围栏封育和翻耕改建下土壤有机碳密度及饱和持水量随恢复年限均表现为对数饱和型的响应特征，退化高寒草甸固碳持水功能的基本恢复年限约为6—10年。春季休牧、秋季休牧、畜群结构优化、减畜轮牧、围栏封育等放牧管理恢复措施应适用于轻度退化至重度退化的高寒草甸，而翻耕改建则是极度退化高寒草甸的适宜治理措施。由于多途径恢复措施的关注目标不同，今后研究应集中在恢复措施的组合优化和综合评价等方面。     

猫颈动脉区压力和化学感受性刺激对巨细胞旁外侧核单位放电的影响

在31只氯醛糖和氨基甲酸乙酯麻醉的猫,观察了选择性激活颈动脉压力和化学感受器对巨细胞旁外侧核(PGL)单位放电的影响。136个PGL自发放电单位中,有84个在激活颈动脉压力感受器(BA)(新福林,1—2μg/kg,iv)和/或激活颈动脉化学感受器(CA)(nicotine 5—20μg,溶于0.25—0.5ml生理盐水中,注入甲状腺动脉)时,放电频率有变化。在这些有反应的单位中,16个仅对CA起反应(11个兴奋、5个抑制);54个以各种组合方式对CA和BA都起反应,其中以CA引起兴奋反应而BA引起抑制反应的占比例最大;14个仅对BA起反应(7个兴奋,7个抑制)。在定位分布上,那些只对CA起反应的单位多位于PGL的腹侧部份;仅对BA起反应的单位则位于对CA起反应单位的较背侧;对BA和CA均起反应的单位介于上述两者之间或在较深区域。这些结果表明,颈动脉区压力和化学感受器活动传入到PGL,并会聚在其中一些神经元上。 在PGL内全部有反应的单位中,68个对激活颈动脉压力感受器起反应,其中兴奋的29个,抑制的39个(P>0.05);70个对激活颈动脉化学感受器起反应,其中48个兴奋,22个抑制(P<0.005)。这些结果提示,BA对PGL神经元引起兴奋和抑制两种效应,而CA则诱发兴奋为主的反应。