外源性的电磁干预对神经病理性疼痛大鼠的镇痛效果研究

目的:探讨外源性的电磁干预方法对神经病理性疼痛大鼠的镇痛效果。方法:将30只成熟的雄性SD大鼠随机等分成3组:空白对照组(Control),坐骨神经慢性压迫损伤(CCI)组以及坐骨神经慢性压迫损伤协同电磁刺激组(CCI+EMF)。CCI组和CCI+EMF组的20只大鼠建立坐骨神经慢性压迫损伤模型,CCI+EMF组大鼠行外源性的全身性电磁刺激干预(脉冲波形,频率15 Hz,强度30 Gs),每天刺激6小时。在CCI模型构建的第0、3、6、9、12及15天对大鼠测试和比较足底机械痛阈值、足底热痛阈值、运动功能评分和神经传导速率。结果:CCI组大鼠的足底机械痛阈值、足底热痛阈值及感觉神经传导速率从CCI手术后的第3天即出现显著性降低,其6、9、12、15天足底机械痛阈值、足底热痛阈值及感觉神经传导速率均显著低于Control组(P0.01),而运动功能评分均显著高于Control组(P0.05)。CCI+EMF组大鼠的足底机械痛阈值、足底热痛阈值及感觉神经传导速率在第9、12、15天显著高于CCI组大鼠(P0.05),而运动功能评分均显著高于CCI l组。结论:外源性的电磁刺激对于神经病理性疼痛大鼠具有良好的镇痛效果,有望成为一种临床治疗神经病理性疼痛的新的物理治疗手段。     

不同全血过滤方法用于去白细胞血液制备的临床对照研究

目的:观察不同全血过滤方法用于去白细胞血液制备的效果。方法:采用两种全血过滤方法进行对比研究,对照组采用常规法,将采集后全血混匀后直接与白细胞滤器连接直接过滤;实验组采用湿润滤盘法,血液采集完成混匀后静置,先用上层血清10～20 m L湿润滤盘,再混匀与白细胞滤器连接后进行过滤。比较两组制备方法所用的过滤时间、血液回收率、过滤前后血液指标情况及24小时内溶血的发生情况。结果:两组全血过滤方法过滤前后白细胞、红细胞、血红蛋白、血小板及血浆游离血红蛋白水平比较差异均无明显统计学意义(P0.05)。而实验组过滤时间短于对照组,血液回收率高于对照组,且24小时内溶血比例明显低于对照组(P0.05)。结论:常规法与湿润滤盘法均能达到去白细胞血液标准,但湿润滤盘法较常规法能有效的降低过滤时间、增加血液回收率,减少去白细胞悬浮红细胞因溶血造成的血液不合格率,值得临床推广应用。     

Doxorubicin‐induced cardiotoxicity is maturation dependent due to the shift from topoisomerase IIα to IIβ in human stem cell derived cardiomyocytes

Doxorubicin (DOX) is widely used to treat various cancers affecting adults and children; however, its clinical application is limited by its cardiotoxicity. Previous studies have shown that children are more susceptible to the cardiotoxic effects of DOX than adults, which may be related to different maturity levels of cardiomyocyte, but the underlying mechanisms are not fully understood. Moreover, researchers investigating DOX‐induced cardiotoxicity caused by human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) have shown that dexrazoxane, the recognized cardioprotective drug for treating DOX‐induced cardiotoxicity, does not alleviate the toxicity of DOX on hiPSC‐CMs cultured for 30 days. We have suggested that this may be ascribed to the immaturity of the 30 days hiPSC‐CMs. In this study, we investigated the mechanisms of DOX induced cardiotoxicity in cardiomyocytes of different maturity. We selected 30‐day‐old and 60‐day‐old hiPSC‐CMs (day 30 and day 60 groups), which we term ‘immature’ and ‘relatively mature’ hiPSC‐CMs, respectively. The day 30 CMs were found to be more susceptible to DOX than the day 60 CMs. DOX leads to more ROS (reactive oxygen species) production in the day 60 CMs than in the relatively immature group due to increased mitochondria number. Moreover, the day 60 CMs mainly expressed topoisomerase IIβ presented less severe DNA damage, whereas the day 30 CMs dominantly expressed topoisomerase IIα exhibited much more severe DNA damage. These results suggest that immature cardiomyocytes are more sensitive to DOX as a result of a higher concentration of topoisomerase IIα, which leads to more DNA damage.     

Stilbene Glycoside Oligomers from the Roots of Polygonum multiflorum

Five new trans‐2,3,5,4′‐tetrahydroxystilbene 2‐O‐β‐d ‐glucopyranoside (TSG)‐based stilbene glycoside oligomers ( 1 – 5 ) were isolated from the roots of Polygonum multiflorum. Their structures were elucidated by comprehensive spectroscopic analyses and chemical evidences. The absolute configurations of 1 , 2 , 4 , and 5 were established by quantum‐chemical electronic circular dichroism (ECD) calculations. Putative biosynthetic pathways of 1–5 were proposed using TSG as the key precursor. In addition, compounds 1 (multiflorumiside H) and 3 (multiflorumiside J) exhibited moderate inhibitory activities against NO production in LPS‐stimulated RAW264.7 cells.     

Patterned Wettability Surface for Competition‐Driving Large‐Grained Perovskite Solar Cells

Novel photovoltaic perovskite solar cells (PSCs) with high‐efficient photovoltaic property are largely in thrall to the uncertain perovskite grain size and inevitable defects. Here, inspired by the competitive growth between tree and grass in the forest system, a competitive perovskite grain growth approach via micro‐contact print (MicroCP) method (CD disk as templates) for printing wettability‐patterned substrate is proposed, aiming to achieve large‐grained perovskite and avoid discontinuous perovskite films caused by the low wettability of substrates. A MicroCP process is employed to construct a patterned wettability surface for the perovskite competitive growth mechanism on the electrode surface. This approach modifies the substrates quickly, ensures the uniform coverage of perovskite due to the function of ‐NH₂ and Pb²⁺ bonds, and converts the perovskite films composed of small grains and pinholes into high‐quality perovskite films, free from pinholes and made up of large grains, resulting in efficiencies over 20% for the MicroCP PSCs.     

Disruptor of telomeric silencing 1-like (DOT1L) is involved in breast cancer metastasis via transcriptional regulation of MALAT1 and ZEB2

<正>Epigenetics refers to how chromatin-associated factors and reversible chromatin modifications maintain DNA-based programs by regulating the chromatin structure (Strahl and Allis,2000).In recent years,genome sequencing studies of cancer have shown that genes encoding epigenetic factors are commonly mutated in cancer(Garraway and Lander,2013).Dys regulated,or mutant,epigenetic factors influence tumorigenesis progression (Dawson and Kouzarides,     

Human NOC3 is essential for DNA replication licensing in human cells

Noc3p (Nucleolar Complex-associated protein) is an essential protein in budding yeast DNA replication licensing. Noc3p mediates the loading of Cdc6p and MCM proteins onto replication origins during the M-to-G₁ transition by interacting with ORC (Origin Recognition Complex) and MCM (Minichromosome Maintenance) proteins. FAD24 (Factor for Adipocyte Differentiation, clone number 24), the human homolog of Noc3p (hNOC3), was previously reported to play roles in the regulation of DNA replication and proliferation in human cells. However, the role of hNOC3 in replication licensing was unclear. Here we report that hNOC3 physically interacts with multiple human pre-replicative complex (pre-RC) proteins and associates with known replication origins throughout the cell cycle. Moreover, knockdown of hNOC3 in HeLa cells abrogates the chromatin association of other pre-RC proteins including hCDC6 and hMCM, leading to DNA replication defects and eventual apoptosis in an abortive S-phase. In comparison, specific inhibition of the ribosome biogenesis pathway by preventing pre-rRNA synthesis, does not lead to any cell cycle or DNA replication defect or apoptosis in the same timeframe as the hNOC3 knockdown experiments. Our findings strongly suggest that hNOC3 plays an essential role in pre-RC formation and the initiation of DNA replication independent of its potential role in ribosome biogenesis in human cells.