Distinct Expression Patterns of Cxcl12 in Mesenchymal Stem Cell Niches of Intact and Injured Rodent Teeth

Specific stem cell populations within dental mesenchymal tissues guarantee tooth homeostasis and regeneration throughout life. The decision between renewal and differentiation of stem cells is greatly influenced by interactions with stromal cells and extracellular matrix molecules that form the tissue specific stem cell niches. The Cxcl12 chemokine is a general marker of stromal cells and plays fundamental roles in the maintenance, mobilization and migration of stem cells. The aim of this study was to exploit Cxcl12-GFP transgenic mice to study the expression patterns of Cxcl12 in putative dental niches of intact and injured teeth. We showed that endothelial and stromal cells expressed Cxcl12 in the dental pulp tissue of both intact molars and incisors. Isolated non-endothelial Cxcl12⁺ dental pulp cells cultured in different conditions in vitro exhibited expression of both adipogenic and osteogenic markers, thus suggesting that these cells possess multipotent fates. Taken together, our results show that Cxcl12 is widely expressed in intact and injured teeth and highlight its importance as a key component of the various dental mesenchymal stem cell niches.     

If Virchow and Ehrlich Had Dreamt Together: What the Future Holds for KRAS-Mutant Lung Cancer

Non-small-cell lung cancer (NSCLC) with Kirsten rat sarcoma (KRAS) mutations has notoriously challenged oncologists and researchers for three notable reasons: (1) the historical assumption that KRAS is “undruggable”, (2) the disease heterogeneity and (3) the shaping of the tumor microenvironment by KRAS downstream effector functions. Better insights into KRAS structural biochemistry allowed researchers to develop direct KRAS(G12C) inhibitors, which have shown early signs of clinical activity in NSCLC patients and have recently led to an FDA breakthrough designation for AMG-510. Following the approval of immune checkpoint inhibitors for PDL1-positive NSCLC, this could fuel yet another major paradigm shift in the treatment of advanced lung cancer. Here, we review advances in our understanding of the biology of direct KRAS inhibition and project future opportunities and challenges of dual KRAS and immune checkpoint inhibition. This strategy is supported by preclinical models which show that KRAS(G12C) inhibitors can turn some immunologically “cold” tumors into “hot” ones and therefore could benefit patients whose tumors harbor subtype-defining STK11/LKB1 co-mutations. Forty years after the discovery of KRAS as a transforming oncogene, we are on the verge of approval of the first KRAS-targeted drug combinations, thus therapeutically unifying Paul Ehrlich’s century-old “magic bullet” vision with Rudolf Virchow’s cancer inflammation theory.     

Adenosine Receptor Agonist HE-NECA Enhances Antithrombotic Activities of Cangrelor and Prasugrel in vivo by Decreasing of Fibrinogen Density in Thrombus

Blood platelets’ adenosine receptors (AR) are considered to be a new target for the anti-platelet therapy. This idea is based on in vitro studies which show that signaling mediated by these receptors leads to a decreased platelet response to activating stimuli. In vivo evidence for the antithrombotic activity of AR agonists published to date were limited, however, to the usage of relatively high doses given in bolus. The present study was aimed at verifying if these substances used in lower doses in combination with inhibitors of P2Y₁₂ could serve as components of dual anti-platelet therapy. We have found that a selective A_2A agonist 2-hexynyl-5’-N-ethylcarboxamidoadenosine (HE-NECA) improved the anti-thrombotic properties of either cangrelor or prasugrel in the model of ferric chloride-induced experimental thrombosis in mice. Importantly, HE-NECA was effective not only when applied in bolus as other AR agonists in the up-to-date published studies, but also when given chronically. In vitro thrombus formation under flow conditions revealed that HE-NECA enhanced the ability of P2Y₁₂ inhibitors to decrease fibrinogen content in thrombi, possibly resulting in their lower stability. Adenosine receptor agonists possess a certain hypotensive effect and an ability to increase the blood–brain barrier permeability. Therefore, the effects of anti-thrombotic doses of HE-NECA on blood pressure and the blood–brain barrier permeability in mice were tested. HE-NECA applied in bolus caused a significant hypotension in mice, but the effect was much lower when the substance was given in doses corresponding to that obtained by chronic administration. At the same time, no significant effect of HE-NECA was observed on the blood–brain barrier. We conclude that chronic administration of the A_2A agonist can be considered a potential component of a dual antithrombotic therapy. However, due to the hypotensive effect of the substances, dosage and administration must be elaborated to minimize the side-effects. The total number of animals used in the experiments was 146.     

冷热循环工艺中冷热转移速率对LY12铝合金尺寸稳定性的影响

研究了冷热转移速率对LY1 2铝合金微屈服强度和残余应力的影响。结果表明 ,提高冷热转移速率易使材料中形成稳定的位错组态 ,从而有利于提高微屈服强度 ;对于圆柱和圆环试样 ,提高冷热转移速率不利于降低残余应力。分析认为 ,冷热转移速率应根据工件几何形状和尺寸进行相应调整。     

提高Cr12MoV钢冷作模具寿命的措施

从原材料改锻、预备热处理、淬火及回火、深冷处理、表面强化处理等方面分析介绍了提高Cr12MoV钢冷作模具寿命的一些方法和措施 ,并通过实例表明 ,采用这些方法和措施可较大幅度地提高模具寿命     

模具钢深冷处理的应用研究

研究了Cr12MoV钢拉深凸模经不同工艺热处理后的性能变化。结果表明，深冷处理是提高模具寿命的可靠途径。     

Electrochemical and analytical study of corrosion inhibition on carbon steel in HCl medium by 1,12-bis(1,2,4-triazolyl)dodecane

1,12-bis(1,2,4-triazolyl)dodecane (dTC12) is an excellent corrosion inhibitor for carbon steel in deaerated 1 M HCl solution. In this work electrochemical and analytical techniques were used to study the inhibition of corrosion on carbon steel in acidic medium. The carbon steel corrosion inhibition of dTC12 was attributed to the synergistic effect between chloride anion and quaternary ammonium ion. The protective efficiency of the film was higher than 90%, indicating that corrosion of carbon steel in 1 M HCl is reduced by dTC12.The effect of dissolved oxygen on the inhibition efficiency was also investigated. The results show that the inhibition efficiency increases in early stage and decreases for a long immersion time.     

汽轮机叶片用1Cr12Mo钢成分与热处理工艺对冲击韧度的影响

1Cr12Mo钢属于马氏体不锈钢，被广泛用于汽轮机亚临界机组的低压叶片。该钢在生产过程中由于冶炼方法的不同其化学成分会在一定范围内变化。对大量生产和试验数据进行分析的结果表明，成分的波动和热处理工艺参数的变化对钢的冲击韧度都有重要的影响。     

机械合金化Al—12Ti—6Nb合金的热稳定性

将机械合金化（ＭＡ）Ａｌ－１２Ｔｉ－６Ｎｂ合金在５５０℃下空气中长时间暴露后，用光学显微镜和电子探针对其组织结构变化进行了观察与分析，测定了维氏硬度。结果表明，ＭＡＡｌ－１２Ｔｉ－６Ｎｂ表现出良好的热稳定性，在５５０℃下暴露２００ｈ后，Ａｌ３Ｔｉ中的亚稳的α－Ｔｉ核才全部转变为Ａｌ３Ｔｉ，Ａｌ３Ｔｉ颗粒随之粗化，饼状的Ａｌ３Ｔｉ变成椭球体；Ａｌ３Ｔｉ颗粒的粗化是通过Ｔｉ，Ａｌ原子扩散所控制的α－Ｔ     

ADC12铝合金在水蒸汽中的腐蚀行为

铸态和固溶化处理的ADC12铝合金在90℃水蒸汽中的腐蚀试验表明：铸态铝合金基体腐蚀是以Al-Cu为基的第二相化合物，而以Al-Fe为基的化合物不会引起基体腐蚀；经固溶化处理的铝合金基体腐蚀是由Al-Fe为基的化合物引起的，并且是以含Cu的Al-Fe化合物周围优先被腐蚀。