Cognitive Changes during Prolonged Stay at High Altitude and Its Correlation with C-Reactive Protein

Hypersensitive C-reaction protein (hsCRP) may be a risk factor for cognitive impairment resulting from Alzheimer’s disease (AD), stroke, and vascular dementia. This study explored the correlation of peripheral blood hsCRP level with cognitive decline due to high altitude exposure. The study was conducted on 100 male military participants who had never been to high altitude. Cerebral oxygen saturation monitoring, event related potentials (P300, N200) detection, and neurocognitive assessment was performed and total hsCRP, interleukin-6 (IL-6), and homocysteine was estimated at 500m altitude, 3650m altitude, 3day, 1, and 3 month post arriving at the base camp (4400m), and 1 month after coming back to the 500m altitude. High altitude increased brain oxygen saturation, prolonged P300 and N200 latencies, injured cognitive functions, and raised plasma hsCRP levels. But they all recovered in varying degrees at 1 and 3 month post arriving at the base camp (4400m). P300 latencies and hsCRP levels were strongly correlated to cognitive performances. These results suggested that cognitive deterioration occurred during the acute period of exposure to high altitude and may recover probably owning to acclimatization after extended stay at high altitude. Plasma hsCRP is inversely correlated to neurological cognition and it may be a potential biomarker for the prediction of high altitude induced cognitive dysfunction.     

Small Molecule Proprotein Convertase Inhibitors for Inhibition of Embryo Implantation

Uterine proprotein convertase (PC) 6 plays a critical role in embryo implantation and is pivotal for pregnancy establishment. Inhibition of PC6 may provide a novel approach for the development of non-hormonal and female-controlled contraceptives. We investigated a class of five synthetic non-peptidic small molecule compounds that were previously reported as potent inhibitors of furin, another PC member. We examined (i) the potency of these compounds in inhibiting PC6 activity in vitro; (ii) their binding modes in the PC6 active site in silico; (iii) their efficacy in inhibiting PC6-dependent cellular processes essential for embryo implantation using human cell-based models. All five compounds showed potent inhibition of PC6 activity in vitro, and in silico docking demonstrated that these inhibitors could adopt a similar binding mode in the PC6 active site. However, when these compounds were tested for their inhibition of decidualization of primary human endometrial stromal cells, a PC6-dependent cellular process critical for embryo implantation, only one (compound 1o) showed potent inhibition. The lack of activity in the cell-based assay may reflect the inability of the compounds to penetrate the cell membrane. Because compound''s lipophilicity is linked to cell penetration, a measurement of lipophilicity (logP) was calculated for each compound. Compound 1o is unique as it appears the most lipophilic among the five compounds. Compound 1o also inhibited another crucial PC6-dependent process, the attachment of human trophoblast spheroids to endometrial epithelial cells (a model for human embryo attachment). We thus identified compound 1o as a potent small molecule PC6 inhibitor with pharmaceutical potential to inhibit embryo implantation. Our findings also highlight that human cell-based functional models are vital to complement the biochemical and in silico analyses in the selection of promising drug candidates. Further investigations for compound 1o are warranted in animal models to test its utility as an implantation-inhibiting contraceptive drug.     

Comparison Study of Bone Defect Healing Effect of Raw and Processed Pyritum in Rats

To evaluate and compare the effect of raw and processed pyritum on tibial defect healing, 32 male Sprague Dawley rats were randomly divided into four groups. After tibial defect, animals were produced and grouped: sham and control group were orally administrated with distilled water (1 mL/100 g), while treatment groups were given aqueous extracts of raw and processed pyritum (1.5 g/kg) for successive 42 days. Radiographic examination showed that bone defect healing effect of the treatment groups was obviously superior compared to that of the control group. Bone mineral density of whole tibia was increased significantly after treating with pyritum. Inductively coupled plasma-optical emission spectrometry showed that the contents of Ca, P, and Mg in callus significantly increased in the treatment groups comparing with the control. Moreover, serological analysis showed that the concentration of serum phosphorus of the treatment groups significantly increased compared with that of the control group. By in vitro study, we have evaluated the effects of drug-containing serum of raw and processed pyritum on osteoblasts. It was manifested that both the drug-containing sera of raw and processed pyritum significantly increased the mRNA levels of alkaline phosphatase and collagen type I. Protein levels of phosphorylated Smad2/3 also increased. The mRNA levels of osteocalcin and transforming growth factor β (TGF-β) type I and II receptors, as well as the protein levels of TGF-β1 in the processed groups, were higher than those in the control. In summary, both raw and processed pyritum-containing sera exhibited positive effects on osteoblasts, which maybe via the TGF-β1/Smad signaling pathway. Notably, the tibia defect healing effect of pyritum was significantly enhanced after processing.     

20世纪90年代以来中国生态空间演化的时空格局和梯度效应

改革开放以来中国经济和城市化的快速发展促使生产和生活空间挤占大量生态空间，系统认识和评估我国生态空间演化的宏观格局和过程对于生态文明建设具有重要的理论和现实意义。为揭示全国生态空间变化的时空过程，在对生态空间内涵进行界定的基础上，结合全国尺度时序土地利用数据构建生态空间分类体系，并评估1990-2015年中国生态空间演化特征。结果表明：1990-2015年中国生态用地面积持续减少，主要向半生态用地转变，发生在重要的粮食生产区域及周边；半生态用地面积波动明显，前期主要表现为不断扩张，后期大量转换为弱生态用地，发生在主要城市群地区；弱生态用地持续扩张，与城镇化进程不断加速相关。中国生态空间演变过程表现出一定的区域差异和梯度效应，不同区域生态空间变化发生的拐点时间有所不同，呈现"自东向西、由南到北"的3级梯度特征，区域生态空间状况与经济发展战略及生态空间管控具有较强的相关性。本研究对于国家生态空间管控近远期战略方案制订具有一定启示，建议处于不同梯度的各地区应基于区域生态空间演化所处阶段和不同驱动机制，确定分区域生态空间安全红线目标和生态空间管控方案。     

The oncolytic peptide LTX-315 triggers necrotic cell death

The oncolytic peptide LTX-315 has been designed for killing human cancer cells and turned out to stimulate anti-cancer immune responses when locally injected into tumors established in immunocompetent mice. Here, we investigated the question whether LTX-315 induces apoptosis or necrosis. Transmission electron microscopy or morphometric analysis of chromatin-stained tumor cells revealed that LTX-315 failed to induce apoptotic nuclear condensation and rather induced a necrotic phenotype. Accordingly, LTX-315 failed to stimulate the activation of caspase-3, and inhibition of caspases by means of Z-VAD-fmk was unable to reduce cell killing by LTX-315. In addition, 2 prominent inhibitors of regulated necrosis (necroptosis), namely, necrostatin-1 and cycosporin A, failed to reduce LTX-315-induced cell death. In conclusion, it appears that LTX-315 triggers unregulated necrosis, which may contribute to its pro-inflammatory and pro-immune effects.     

Fish technology in chromosome and genome research

Fluorescent in situ hybridization technology is one of the most exciting and versatile research tools to be developed in recent years. It has enabled research to progress at a phenomenal rate in diverse areas of basic research as well as in clinical medicine. Fluorescent in situ hybridization has applications in physical mapping, the study of nuclear architecture and chromatin packaging, and the investigation of fundamental principles of biology such as DNA replication, RNA processing, gene amplification, gene integration and chromatin elimination. This review highlights some of these areas and provides source material for the reader who seeks more information on a specific field.