80例TIA病人的血液流变学分析

目的探讨ＴＩＡ病人的血液流变学改变。方法８０例ＴＩＡ病人均在末次发作后２４ｈ内静脉抽血进行血液流变学测定,并与对照组进行比较。结果ＴＩＡ组病人的红细胞压积、全血高切粘度、全血低切粘度、全血还原高切粘度、全血还原低切粘度、血浆粘度及红细胞聚集性各指标均明显增高,与正常对照组比较有显著性差异。结论血液粘度的增高是引起短暂性脑缺血发作的发病机制之一。     

The X-ray structure of an antiparallel dimer of the human amyloid precursor protein E2 domain

Amyloid beta-peptide, which forms neuronal and vascular amyloid deposits in Alzheimer's disease, is derived from an integral membrane protein precursor. The biological function of the precursor is currently unclear. Here we describe the X-ray structure of E2, the largest of the three conserved domains of the precursor. The structure of E2 consists of two coiled-coil substructures connected through a continuous helix and bears an unexpected resemblance to the spectrin family of protein structures. E2 can reversibly dimerize in the solution, and the dimerization occurs along the longest dimension of the molecule in an antiparallel orientation, which enables the N-terminal substructure of one monomer to pack against the C-terminal substructure of a second monomer. Heparan sulfate proteoglycans, the putative ligand for the precursor present in extracellular matrix, bind to E2 at a conserved and positively charged site near the dimer interface.     

Single‐Atom to Single‐Atom Grafting of Pt1 onto FeN4 Center: Pt1@FeNC Multifunctional Electrocatalyst with Significantly Enhanced Properties

Nonprecious metal catalysts (NPMCs) Fe?N?C are promising alternatives to noble metal Pt as the oxygen reduction reaction (ORR) catalysts for proton‐exchange‐membrane fuel cells. Herein, a new modulation strategy is reported to the active moiety Fe?N₄ via a precise “single‐atom to single‐atom” grafting of a Pt atom onto the Fe center through a bridging oxygen molecule, creating a new active moiety of Pt₁?O₂?Fe₁?N₄. The modulated Fe?N?C exhibits remarkably improved ORR stabilities in acidic media. Moreover, it shows unexpectedly high catalytic activities toward oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), with overpotentials of 310 mV for OER in alkaline solution and 60 mV for HER in acidic media at a current density of 10 mA cm^?2, outperforming the benchmark RuO₂ and comparable with Pt/C(20%), respectively. The enhanced multifunctional electrocatalytic properties are associated with the newly constructed active moiety Pt₁?O₂?Fe₁?N₄, which protects Fe sites from harmful species. Density functional theory calculations reveal the synergy in the new active moiety, which promotes the proton adsorption and reduction kinetics. In addition, the grafted Pt₁?O₂? dangling bonds may boost the OER activity. This study paves a new way to improve and extend NPMCs electrocatalytic properties through a precisely single‐atom to single‐atom grafting strategy.     

miR-152/TNS1 axis inhibits non-small cell lung cancer progression through Akt/mTOR/RhoA pathway

Aim: The purpose of the present study was to explore the function and mechanism of tensin 1 (TNS1) in non-small cell lung cancer (NSCLC) progression.Methods: The expression of TNS1 in NSCLC cells and tissues was assessed by RT-PCR and Western blot. Besides, Kaplan–Meier survival analysis was recruited to explore the association between TNS1 and NSCLC. Cell growth was analyzed by MTT and flow cytometry assay, while cell metastasis was determined by wound healing and transwell assays. The targeting relationship between TNS1 and miR-152 was assessed by luciferase activity assays. And Western blot was employed to determine the expression of related proteins of Akt/mTOR/RhoA pathway.Results: TNS1 level was boosted in NSCLC cells and tissues, related to the prognosis of NSCLC patients. Furthermore, it was proved that TNS1 promoted the growth and metastasis of NSCLC cells via Akt/mTOR/RhoA pathway. And miR-152 targeted TNS1 to affect the progression of NSCLC.Conclusion: miR-152/TNS1 axis inhibits the progression of NSCLC by Akt/mTOR/RhoA pathway.     

DOT1L Inhibition Sensitizes MLL-Rearranged AML to Chemotherapy

DOT1L, the only known histone H3-lysine 79 (H3K79) methyltransferase, has been shown to be essential for the survival and proliferation of mixed-linkage leukemia (MLL) gene rearranged leukemia cells, which are often resistant to conventional chemotherapeutic agents. To study the functions of DOT1L in MLL-rearranged leukemia, SYC-522, a potent inhibitor of DOT1L developed in our laboratory, was used to treat MLL-rearranged leukemia cell lines and patient samples. SYC-522 significantly inhibited methylation at H3K79, but not H3K4 or H3K27, and decreased the expression of two important leukemia-relevant genes, HOXA9 and MEIS1, by more than 50%. It also significantly reduced the expression of CCND1 and BCL2L1, which are important regulators of cell cycle and anti-apoptotic signaling pathways. Exposure of MLL-rearranged leukemia cells to this compound caused cell cycle arrest and promoted differentiation of those cells, both morphologically and by increased CD14 expression. SYC-522 did not induce apoptosis, even at 10 µM for as long as 6 days. However, treatment with this DOT1L inhibitor decreased the colony formation ability of primary MLL-rearranged AML cells by up to 50%, and promoted monocytic differentiation. Notably, SYC-522 treatment significantly increased the sensitivity of MLL-rearranged leukemia cells to chemotherapeutics, such as mitoxantrone, etoposide and cytarabine. A similar sensitization was seen with primary MLL-rearranged AML cells. SYC-522 did not affect chemotherapy-induced apoptosis in leukemia cells without MLL-rearrangement. Suppression of DOT1L activity inhibited the mitoxantrone-induced increase in the DNA damage response marker, γH2AX, and increased the level of cPARP, an intracellular marker of apoptosis. These results demonstrated that SYC-522 selectively inhibited DOT1L, and thereby altered gene expression, promoted differentiation, and increased chemosensitivity by preventing DNA damage response. Therefore, inhibition of DOT1L, in combination with DNA damaging chemotherapy, represents a promising approach to improving outcomes for MLL-rearranged leukemia.     

透明质酸微针经皮递送胰岛素智能给药系统用于糖尿病治疗

本研究通过共沉淀法制备了胰岛素(insulin,INS)/Ca₃PO₄复合物和葡萄糖氧化酶(glucose oxidase,GOx)/Cu₃(PO₄)₂复合物,得到的矿化胰岛素(mineralized insulin,m-INS)呈现不规则结晶团簇状,矿化葡萄糖氧化酶(m-Gox)呈花球状形貌,直径约1–2 μm。体外模拟释放实验表明,m-INS会随介质pH值降低而释放出INS,pH为4.5时其释放量达到96.68%;酶活力检测实验表明m-GOx的酶活力稳定性高于游离的GOx,在室温放置10 d后仍保持较高活力,而GOx活力小于60%。通过配制葡萄糖溶液模拟正常血糖(5.6 mmol/L)和高血糖(22.2 mmol/L)状态,在葡萄糖溶液中加入m-INS和m-GOx,INS的释放量呈现显著的葡萄糖浓度依赖性,即葡萄糖浓度越高,INS释放量和释放速率越大。最后,将m-INS、m-GOx与透明质酸(hyaluronic acid,HA)溶液混合,制备负载m-INS和m-GOx的HA微针阵列,构建1型糖尿病模型鼠,通过微针给药的方式评估载药HA微针对糖尿病大鼠的血糖控制效果。结果表明：负载m-INS/m-GOx的HA微针能有效递送药物,糖尿病大鼠的平均血糖浓度在1 h内下降到约7 mmol/L,并能维持10 h的正常血糖,使血糖浓度低于给药前水平长达36 h。与仅负载INS的HA微针相比,m-INS微针具有更好的葡萄糖耐受性、更持久的控糖效果和更小的低血糖风险。相对于其他的缓释系统,本研究中的核心成分制备流程简单、效率高和安全有效,具备较大的商业化潜力。     

华北地区夏玉米土壤硝态氮的时空动态与残留

为了进一步明确华北地区冬小麦-夏玉米种植体系周年氮肥利用效率及其影响因素与机制,在试验区夏玉米生育期年均降雨量400mm左右,轻壤质底粘潮土中等土壤肥力条件下,通过设计不同施氮量(0、90、180、270kgN/hm2)处理,重点研究了夏玉米大田土壤硝态氮动态与残留积累情况。试验结果表明,夏玉米根系生物量最大值出现在吐丝期,最大根系分布深度约为1.2m。根干重密度(g/m3)随土壤深度增加而明显降低。根群主要分布在表土层,0～80cm土体根重比例达95%以上,1m以下根重比例不足1%。土壤硝态氮测定表明,从播种前到收获期,各施氮量处理(0、90、180、270kgN/hm2)2m土体土壤硝态氮平均含量均表现出“N”型曲线变化趋势。在玉米收获期,施氮处理(90～270kgN/hm2)2m土体均有明显的硝态氮残留积累,并且残留积累量随着施氮量增加而增大,施氮处理下层土壤(120～200cm)硝态氮残留积累量比不施氮处理高出50.4～95.4kgNO3-N/hm2。这说明,在玉米生育期降水影响下氮肥发生了淋溶,有部分氮肥已经向下移出玉米根区以外,积累在下层土壤中。这些残留积累在下层土壤中的硝态氮对于玉米来说很难被吸收利用,不仅降低了氮肥的利用率,也成为污染地下水的潜在隐患。分析表明,各施氮处理籽粒产量和植株吸氮量都显著大于不施氮处理,但施氮处理之间比较,籽粒产量和植株吸氮量并无显著差异。90kgN/hm2、180kgN/hm2和270kgN/hm2施氮处理下,氮肥表观利用率分别为11.52%、13.37%、9.93%。根据本研究结果,从小麦-玉米种植体系考虑,玉米根区以下残留积累氮素的回收利用是提高周年氮肥利用率的一个重要方面,值得进一步研究。     

节水栽培冬小麦对下层土壤残留氮素的利用

为了进一步明确华北地区冬小麦-夏玉米种植体系周年氮肥利用效率及其影响因素与机制,试验在大田和原状土柱条件下进行了深层土壤放置15N标记氮肥试验,重点研究节水栽培冬小麦对夏玉米生育期淋洗到下层土壤的氮素利用能力。试验结果表明,大田条件下冬小麦根系空间分布与夏玉米存在明显差异,冬前苗期根系下扎深度可达1.0m,开花期最大根深已经超过2.0m。而且,小麦节水栽培(春季不灌水、春季灌2次水)相对于传统充分灌水模式(春季灌4次水)明显提高了根群中的下层根系比例。大田春不灌水和春灌2水条件下,冬小麦对于100~200cm深层土壤放置的15N标记氮肥均能吸收利用。土柱条件下15N标记氮肥试验进一步验证了春灌2水条件下小麦对深层土壤氮素的吸收作用,并表明植株对100~110cm、120~130cm、140~150cm各层土壤标记15N的回收率分别为16.26%、7.33%和4.38%。研究表明,节水栽培促进冬小麦根系深扎,较多的深层根系增强了小麦对深层土壤氮素的吸收和利用能力,有利于截获夏玉米季淋溶到下层土体的肥料氮,从而可减少肥料氮损失。     

Effects of dietary grape pomace on the intestinal microbiota and growth performance of weaned piglets

ABSTRACT

Grape pomace (GP) is an abundant by-product from wine production and is rich in phenolic compounds, unsaturated fatty acids, dietary fibre and beneficial bacteria. In this study, weaned piglets were fed a basic diet supplemented with 5% GP for 4 weeks. Compared with those in the control (CON) group, it was found that the proportion of Lactobacillus delbrueckii, Olsenella umbonata and Selenomonas bovis in the caecum and the villus height and villus height/crypt depth ratio (VCR) of the jejunum were both significantly increased in the GP group (p < 0.05). Meanwhile, at the mRNA expression level, several proinflammatory cytokines (IL-1β, IL-8, IL-6 and TNF-α) were significantly downregulated (p < 0.05) in piglet caecal tissue, and the short-chain fatty acid receptors (GPR41 and GPR43) were not significantly upregulated. In contrast, the levels of IgG was significantly increased (p < 0.05) in the sera of weaned piglets in the GP group. However, no difference in growth performance between the two groups of piglets was detected. These results show that GP had no adverse effects on the growth performance of piglets, but GP can promote the content of some beneficial bacteria in the caecum; this effect is conducive to improving the disease resistance potential of piglets.