BACKGROUND & AIMS: :We carried out sequential molecular monitoring of different markers on two BCR-ABL positive ALL patients receiving a standard dose induction regimen, which was followed by a maintenance therapy that alternated imatinib and chemotherapy administration. Molecular study was performed at diagnosis, at the end of the induction phase, and then every three months during maintenance therapy. Each marrow sample underwent BCR-ABL analysis (p210 and p190 expression by RT-PCR and Real-time PCR) and monoclonal JH rearrangement analysis, while WT1 gene expression was detected by Real-time PCR. At diagnosis we detected high WT1 expression associated with the presence of both BCR-ABL transcripts and monoclonal JH rearrangement in both patients. Hematological remission, as well as a molecular status characterized by undetectable BCR-ABL expression, normal levels of WT1 expression, and persistence of monoclonal JH rearrangement, were achieved by both patients post-therapy. Follow up of patient 1 showed a progressive increase in WT-1 and in p-190 transcript, which was followed by cytogenetic and hematological relapse. We observed a progressive increase in the p210 transcript without a concomitant increase in WT-1 levels in patient 2. JH rearrangement was detected in all the samples analyzed. The molecular results may indicate the persistence of JH rearranged clonal cells with undetectable BCR-ABL. From a clinical point of view, our preliminary experience suggests that simultaneous analysis of BCR-ABL, JH and WT-1 expression may improve the study of MRD in Ph+ ALL.

背景与目标： : 我们对接受标准剂量诱导方案的两名bcr-abl阳性ALL患者进行了不同标志物的顺序分子监测，随后进行了维持治疗，交替使用伊马替尼和化疗。在诊断时，诱导期结束时进行分子研究，然后在维持治疗期间每三个月进行一次分子研究。每个骨髓样品均进行bcr-abl分析 (通过rt-pcr和实时PCR表达p210和p190) 和单克隆JH重排分析，而通过实时PCR检测WT1基因表达。在诊断时，我们检测到两名患者中WT1的高表达与BCR-ABL转录物和单克隆JH重排的存在有关。两名患者在治疗后均实现了血液学缓解以及以bcr-abl表达无法检测，WT1表达正常水平和单克隆JH重排持续为特征的分子状态。对患者1的随访显示WT-1和p-190转录物的进行性增加，随后是细胞遗传学和血液学复发。我们观察到患者2中p210转录物的逐渐增加，而WT-1水平没有随之增加。在所有分析的样品中均检测到JH重排。分子结果可能表明JH重排的克隆细胞存在无法检测到的bcr-abl。从临床角度来看，我们的初步经验表明，同时分析BCR-ABL，JH和WT-1表达可能会改善Ph ALL中MRD的研究。

BACKGROUND & AIMS: :The original article [1] contains several errors.

背景与目标： : 原始文章 [1] 包含几个错误。

BACKGROUND & AIMS: :Non-small cell lung cancer (NSCLC) represents a difficult condition to treat, due to epidermal growth factor receptor (EGFR) kinase domain mutations, which lead to ligand-independent phosphorylation. Deletion of five amino acids (ELREA) in exon 19 and mutational change from leucine to arginine at position 858 (L858R) are responsible for tyrosine kinase domain aberrant activation. These two common types of EGFR-mutated forms are clinically associated with high response with Tyrosine Kinase Inhibitors (TKI); however, the secondary T790M mutation within the Tyrosine Kinase Domain (TKD) determines a resistance to these EGFR-TKIs. Using molecular dynamic simulation (MD), the present study investigated the architectural changes of wild-type and mutants EGFR's kinase domains in order to detect any conformational differences that could be associated with a constitutively activated state and thus to evaluate the differences between the wild-type and its mutated forms. In addition, in order to evaluate to which extent the EGFR mutations affect its inhibition, Epigallocatechin 3-Gallate (EGCG) and Erlotinib (Erl), known EGFR-TKI, were included in our study. Their binding modes with the EGFR-TK domain were elucidated and the binding differences between EGFR wild-type and the mutated forms were evidenced. The aminoacids mutations directly influence the binding affinity of these two inhibitors, resulting in a different efficacy of Erl and EGCG inhibition. In particular, for the T790M/L858R EGFR, the binding modes of studied inhibitors were compromised by aminoacidic substitution confirming the experimental findings. These results may be useful for novel drug design strategies targeting the dimerization domain of the EGFR mutated forms, thus preventing receptor activation.

背景与目标： : 非小细胞肺癌 (NSCLC) 是一种难以治疗的疾病，这是由于表皮生长因子受体 (EGFR) 激酶结构域突变导致配体非依赖性磷酸化。外显子19中五个氨基酸 (ELREA) 的缺失以及在位置858 (L858R) 从亮氨酸到精氨酸的突变变化是酪氨酸激酶结构域异常激活的原因。这两种常见的EGFR突变形式在临床上与酪氨酸激酶抑制剂 (TKI) 的高反应相关; 然而，酪氨酸激酶结构域 (TKD) 内的继发性T790M突变决定了对这些egfr-tki的抗性。使用分子动力学模拟 (MD)，本研究调查了野生型和突变体EGFR激酶结构域的结构变化，以检测可能与组成型激活状态相关的任何构象差异，从而评估野生型及其突变形式之间的差异。此外，为了评估EGFR突变对其抑制作用的影响程度，我们的研究包括了表观没食子儿茶素3-没食子酸酯 (EGCG) 和厄洛替尼 (Erl) (已知egfr-tki)。阐明了它们与egfr-tk结构域的结合模式，并证明了EGFR野生型与突变形式之间的结合差异。氨基酸突变直接影响这两种抑制剂的结合亲和力，导致Erl和EGCG抑制的功效不同。特别是，对于T790M/L858R EGFR，所研究的抑制剂的结合模式受到氨基酸性取代的损害，证实了实验结果。这些结果可能有助于针对EGFR突变形式的二聚化结构域的新型药物设计策略，从而防止受体激活。

BACKGROUND & AIMS: Calpastatin is the natural specific inhibitor of calpain. Recent research has linked uncontrolled calpain activation to tissue damage after neuronal and cardiac ischemias, traumatic spine and brain injuries, as well as Alzheimer's disease and cataract formation. An imbalance between the activities of calpain and calpastatin is believed to be responsible for the pathological role of calpain. An important key to understanding calpain regulation by calpastatin is to determine, at the molecular level, how calpastatin interacts with calpain to inhibit its enzymatic activity. A 27-residue peptide (DPMSSTYIEELGKREVTIPPKYRELLA) derived from subdomain 1B of the repetitive domains of calpain, named peptide B27-WT, was previously shown to be a potent inhibitor of mu- and m-calpain. In this report, a combination of beta-alanine scanning mutagenesis and kinetic measurements was used to probe, in a quantitative, systematic, and simultaneous fashion, the relative contribution of the amino acid side chain and backbone functionalities to the overall calpain-inhibitory activity of B27-WT. The study identified two "hot spots," Leu(11)-Gly(12) and Thr(17)-Ile(18)-Pro(19), in B27-WT within which the residues critical for inhibitory function are clustered. Mutation of any one of the key residues in either of the two hot spots resulted in a dramatic loss of inhibitory activity. Furthermore, it was shown that a restricted conformation of the Leu(11)-Gly(12) and Thr(17)-Ile(18)-Pro(19) backbones is required for the peptide inhibitory function. These results suggest a plausible model in which the two hot spots are situated at or near the interface(s) of the calpain-calpastatin complex and act in a concerted fashion to inhibit calpain. The information on the specific contribution of the amide bond and side chain of each key residue to the bioactivity of B27-WT will contribute to a better understanding of the mechanism of calpain inhibition and lead to novel and effective therapies based on the specific inhibition of dysregulated or overactivated calpain.

背景与目标： 钙蛋白酶抑制剂是钙蛋白酶的天然特异性抑制剂。最近的研究已将不受控制的钙蛋白酶激活与神经元和心脏缺血后的组织损伤，创伤性脊柱和脑损伤以及阿尔茨海默氏病和白内障形成联系起来。钙蛋白酶和钙蛋白酶的活性之间的不平衡被认为是钙蛋白酶的病理作用的原因。理解钙蛋白酶调节钙蛋白酶的重要关键是在分子水平上确定钙蛋白酶如何与钙蛋白酶相互作用以抑制其酶活性。源自钙蛋白酶重复结构域的亚结构域1B的27残基肽 (DPMSSTYIEELGKREVTIPPKYRELLA)，命名为肽B27-WT，先前被证明是mu-和m-钙蛋白酶的有效抑制剂。在本报告中，结合了 β-丙氨酸扫描诱变和动力学测量，以定量，系统和同时的方式探测氨基酸侧链和主链功能对总钙蛋白酶抑制活性的相对贡献B27-WT。该研究确定了两个 “热点”，即Leu(11)-Gly(12) 和Thr(17)-Ile(18)-Pro(19)，在B27-WT中聚集了对抑制功能至关重要的残基。两个热点中的任何一个关键残基的突变都会导致抑制活性的急剧丧失。此外，已显示肽抑制功能需要Leu(11)-Gly(12) 和Thr(17)-Ile(18)-Pro(19) 骨架的受限构象。这些结果表明了一个合理的模型，其中两个热点位于钙蛋白酶-钙蛋白酶复合物的界面处或附近，并以协同方式抑制钙蛋白酶。关于每个关键残基的酰胺键和侧链对B27-WT生物活性的特定贡献的信息将有助于更好地理解钙蛋白酶抑制的机制，并基于对失调或过度激活的钙蛋白酶的特异性抑制而产生新的有效疗法。

BACKGROUND & AIMS: OBJECTIVES:The purpose of this study was to evaluate the fit of metal ceramic crowns cast in Au-1.6 wt% Ti alloy and investigate the effect of abutment finish line curvature on the fit of crowns. METHODS:Three types of finish line curvature abutments were prepared (1, 3 and 5mm-curvature). For each type of abutment, five metal ceramic crowns of the facial veneered type were fabricated, which were cast in Au-1.6 wt% Ti alloy. Used as controls, another fifteen specimens were made from a commercially available gold alloy. The fit was measured in the as-cast and after porcelain application. RESULTS:In the as-cast specimens, the greater the finish line curvature was, the larger the gaps exhibited at the mesial and distal margins of copings, compared with labial and lingual margins. The distal margin of copings for 5mm-curvature abutments showed the largest gap (35 (7) microm). After porcelain application, the greater was the finish line curvature, the larger the labial marginal gap became (mean 44, 34, 25 microm, respectively, for 5, 3, 1mm-curvature). However, there was no significant difference on marginal gaps between specimens of Au-1.6 wt% Ti alloy and control gold alloy. SIGNIFICANCE:This study indicated that the metal ceramic crowns cast in Au-1.6 wt% Ti alloy had equivalent accuracy to those that cast in control gold alloy, and the abutment finish line curvature had a significant effect on the marginal fit of metal ceramic crowns.

背景与目标：

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :Effect of refining element phosphorus (P) on the morphology of the primary silicon in the Al-70 wt.%Si alloy was investigated via the electromagnetic levitation (EML) technique. The morphology and microstructure were analyzed by using high-speed video (HSV) and scanning electron microscopy (SEM). It was found that the morphology of primary silicon transformed from dendrites with several branches to blocky shape, and then to equiaxed grains in Al-70 wt.%Si and Al-70 wt.%Si-1.0 wt.%P alloys with increasing of undercooling. The nucleation number and nucleation rate increased exponentially with the increase of undercooling for both alloys. Finally, the growth velocity of primary silicon was discussed in combination with classical theory.

背景与目标： : 通过电磁悬浮 (EML) 技术研究了精炼元素磷 (P) 对Al-70 wt。% Si合金中初硅形态的影响。使用高速视频 (HSV) 和扫描电子显微镜 (SEM) 分析了形貌和微观结构。发现随着过冷度的增加，初级硅的形态从具有多个分支的枝晶转变为块状，然后在Al-70 wt。% Si和Al-70。% Si-1.0 wt。% P合金中转变为等轴晶粒。两种合金的成核数和成核速率均随过冷度的增加而呈指数增长。最后，结合经典理论讨论了原硅的生长速度。

BACKGROUND & AIMS: :High salt (HS) dietary intake leads to impaired vascular endothelium-dependent responses to various physiological stimuli, some of which are mediated by arachidonic acid (AA) metabolites. Transgenic Tff3-/- gene knockout mice (Tff3-/-/C57BL/6N) have changes in lipid metabolism which may affect vascular function and outcomes of stroke. We aimed to study the effects of one week of HS diet (4% NaCl) on vascular function and stroke induced by transient occlusion of middle cerebral artery in Tff3-/- and wild type (WT/C57BL/6N) mice. Flow-induced dilation (FID) of carotid artery was reduced in WT-HS mice, but not affected in Tff3-/--HS mice. Nitric oxide (NO) mediated FID. NO production was decreased with HS diet. On the contrary, acetylcholine-induced dilation was significantly decreased in Tff3-/- mice on both diets and WT-HS mice. HS intake and Tff3 gene depletion affected the structural components of the vessels. Proteomic analysis revealed a significant effect of Tff3 gene deficiency on HS diet-induced changes in neuronal structural proteins and acute innate immune response proteins' expression and Tff3 depletion, but HS diet did not increase the stroke volume, which is related to proteome modification and upregulation of genes involved mainly in cellular antioxidative defense. In conclusion, Tff3 depletion seems to partially impair vascular function and worsen the outcomes of stroke, which is moderately affected by HS diet.

背景与目标： : 高盐 (HS) 饮食摄入导致对各种生理刺激的血管内皮依赖性反应受损，其中一些是由花生四烯酸 (AA) 代谢产物介导的。转基因Tff3-/-基因敲除小鼠 (Tff3-/C57BL/6N) 的脂质代谢变化可能会影响血管功能和中风的结局。我们旨在研究一周的HS饮食 (4% NaCl) 对Tff3-/-和野生型 (WT/C57BL/6N) 小鼠大脑中动脉短暂闭塞引起的血管功能和中风的影响。在WT-HS小鼠中，颈动脉的血流诱导扩张 (FID) 减少，但在Tff3-/-HS小鼠中不受影响。一氧化氮 (NO) 介导FID。HS饮食不会减少任何产量。相反，在饮食和WT-HS小鼠中，Tff3-/-小鼠中乙酰胆碱诱导的扩张作用均显着降低。HS摄入和Tff3基因耗竭影响血管的结构成分。蛋白质组学分析显示，Tff3基因缺乏对HS饮食诱导的神经元结构蛋白和急性先天免疫反应蛋白表达的变化以及Tff3耗竭有显着影响，但HS饮食并未增加中风量，这与蛋白质组修饰和上调主要参与细胞抗氧化防御的基因有关。总之，Tff3耗竭似乎部分损害了血管功能并恶化了中风的结局，中风受到HS饮食的适度影响。

BACKGROUND & AIMS: :Recent advances in molecular biology have revolutionized the concept of KIT/PDGFRA wild type (WT) gastrointestinal stromal tumors (GIST) than the past. Indeed, from being defined as GIST without KIT or PDGFRA mutations, we are now faced with the opposite scenario, where KIT/PDGFRA WT GIST are "positively" defined according to their specific molecular alterations. In particular, if until recently KIT/PDGFRA GIST without abnormalities of KIT, PDGFRA, SDH, and the RAS signaling pathway were referred as quadruple WT GIST, today also this small subset of GIST is emerging out as a group of heterogeneous distinct entities with multiple different molecular alterations. Therefore, given this still growing and rapidly evolving scenario, the progressive molecular fragmentation may inevitably lead over the time to the disappearance of KIT/PDGFRA WT GIST, destined to be singularly defined by their molecular fingerprint.

背景与目标： : 分子生物学的最新进展比过去彻底改变了KIT/PDGFRA野生型 (WT) 胃肠道间质瘤 (GIST) 的概念。实际上，从被定义为没有KIT或PDGFRA突变的GIST开始，我们现在面临相反的情况，即KIT/PDGFRA WT GIST根据其特定的分子变化被 “肯定” 定义。特别是，如果直到最近KIT/PDGFRA GIST没有KIT，PDGFRA，SDH和RAS信号通路异常被称为四重WT GIST，那么今天GIST的这一小部分也作为一组异质的不同实体出现，具有多种不同的分子改变。因此，鉴于这种仍在增长和快速发展的情况，渐进的分子断裂可能不可避免地导致随着时间的流逝，KIT/PDGFRA WT GIST的消失，注定要由其分子指纹单独定义。

BACKGROUND & AIMS: :So far >180 mutations have been identified within the 153-residue human SOD1 to cause familial amyotrophic lateral sclerosis (FALS), while wild-type (WT) SOD1 was intriguingly implicated in sporadic ALS (SALS). SOD1 mutations lead to ALS by a dominant gain of cytotoxicity but its mechanism still remains elusive. Previously functional studies have revealed that SOD1 mutants became unexpectedly associated with organelle membranes. Indeed we decoded that the ALS-causing truncation mutant L126Z-SOD1 with an elevated toxicity completely loses the ability to fold into the native β-barrel structure but acquire a novel capacity to interact with membranes by forming helices over hydrophobic/amphiphilic segments. Very recently, the abnormal insertion of SOD1 mutants into ER membrane has been functionally characterized to trigger ER stress, an initial event of a cascade of cell-specific damages in ALS pathogenesis. Here we attempted to understand the mechanism for gain of cytotoxicity of the WT SOD1. We obtained atomic-resolution evidence that the nascent WT SOD1 without metalation and disulfide bridge is also highly disordered as L126Z. Most importantly, it owns the same capacity in interacting with membranes by forming very similar helices over the first 125 residues identical to L126Z-SOD1, plus an additional hydrophobic helix over Leu144-Ala152. Our study thus implies that the WT and mutant SOD1 indeed converge on a common mechanism for gain of cytotoxicity by abnormally interacting with membranes. Moreover, any genetic/environmental factors which can delay or impair its maturation might act to transform SOD1 into cytotoxic forms with the acquired capacity to abnormally interact with membranes.

背景与目标： : 到目前为止，已经在153残基人SOD1中发现了180个突变，导致家族性肌萎缩性侧索硬化症 (fars)，而野生型 (WT) SOD1有趣地与散发性ALS (ALS) 有关。SOD1突变通过细胞毒性的优势获得导致ALS，但其机制仍然难以捉摸。先前的功能研究表明，SOD1突变体与细胞器膜意外相关。实际上，我们解码出毒性升高的ALS引起截断突变体L126Z-SOD1完全失去了折叠成天然 β-桶结构的能力，但通过在疏水/两亲链段上形成螺旋而获得了与膜相互作用的新能力。最近，SOD1突变体异常插入ER膜的功能已被表征为触发ER应激，这是ALS发病机理中细胞特异性损伤级联的初始事件。在这里，我们试图了解获得WT sod1细胞毒性的机制。我们获得了原子分辨率的证据，表明没有金属化和二硫键的新生WT SOD1也与L126Z高度无序。最重要的是，通过在与膜相同的前125个残基上形成非常相似的螺旋，加上在Leu144-Ala152上形成额外的疏水螺旋，它具有与L126Z-SOD1相互作用的相同能力。因此，我们的研究表明，WT和突变体SOD1确实通过与膜异常相互作用而收敛于获得细胞毒性的共同机制。此外，任何可能延迟或损害其成熟的遗传/环境因素都可能将SOD1转化为具有与膜异常相互作用的获得性能力的细胞毒性形式。

BACKGROUND & AIMS: BACKGROUND:Mechanical stress is a key pathogenic driver of apoptosis in the tubular epithelium in obstructive nephropathy. Heat shock protein 70 (Hsp70) and Wilms' tumor (WT-1) have been proposed to represent linked downstream effectors of the cytoprotective properties of NO. In the present study, we sought to evaluate whether the cytoprotective effects of L-arginine in neonatal obstructive nephropathy may be associated with NO-dependent increases in WT-1 and Hsp70 expression. METHODS:Neonatal Wistar-Kyoto rats were submitted to complete unilateral ureteral obstruction (UUO) and treated thereafter with vehicle, L-NAME or L-arginine by daily gavage for 14 days to block or augment NO levels, respectively. Normal rat kidney epithelial cells by NRK-52E were exposed to mechanical stress in vitro in the presence or absence of L-NAME, L-arginine, sodium nitroprusside (SNP), L-arginine + SNP or L-arginine/L-NAME. Induction of apoptosis and the mRNA expression of WT-1 and Hsp70 genes were assessed. RESULTS:WT-1 and Hsp70 genes expression decreased in the presence of L-NAME and following UUO coincident with increased tubular apoptosis. L-arginine treatment increased NO levels, reduced apoptosis and restored expression levels of WT-1 and Hsp70 to control levels. L-arginine treatment in vitro reduced basal apoptotic rates and prevented apoptosis in response to mechanical strain, an effect enhanced by SNP co-incubation. L-NAME increased apoptosis and prevented the anti-apoptotic action of L-arginine. CONCLUSIONS:L-arginine treatment in experimental neonatal UUO reduces apoptosis coincident with restoration of WT-1 and Hsp70 expression levels and directly inhibits mechanical strain-induced apoptosis in an NO-dependent manner in vitro. This potentially implicates an NO-Hsp70-WT-1 axis in the cytoprotective effects of L-arginine.

背景与目标：

BACKGROUND & AIMS: :The negative effects of ambient ultraviolet (UVA) on the water environment have been recently highlighted; UVA can create deleterious effects by stimulating stress on pelagic organisms. Little is known about UVA effects on oocyte characteristics of female fish. In the present study we explored the effects of exposure to ecologically relevant levels of simulated UVA radiation on ovaries of two major strains WT (HdrR) and P53 (-/-) of medaka (Oryzias latipes) mature female. Fish were assigned to control and three UVA-exposed groups as (15 min, 30 min, and 60 min/day) for three days and sample selection was 24 h and 14 days after exposure. Histological alterations and oocyte atresia percentage were analyzed in the UVA-exposed fish compared to control. Alteration comprised hyperthrophied follicular cells with increased thickness, breakdown of egg chorion (zona radiata), damage of cortical alveoli, and distorted nucleus and cytoplasm. The atresia percentages significantly increased with higher UVA exposure dose and time for both the wild type and the p53 deficient fish. The wild type displayed significantly higher oocyte atresia percentage than the p53 mutant. These results suggested that UVA exposure provoked histological alterations in both p53 and WT medaka oocytes leading to follicular atresia, which reduce female reproductive ability and larval production. UVA oocyte response showed p53 dependent and independent histological alteration, however, the p53 mutant was less sensitive to UVA than the wild type in medaka fish.

背景与目标： : 最近强调了环境紫外线 (UVA) 对水环境的负面影响; UVA可以通过刺激对中上层生物的压力来产生有害影响。关于UVA对雌鱼卵母细胞特征的影响知之甚少。在本研究中，我们探索了暴露于模拟UVA辐射的生态相关水平对medaka (Oryzias latipes) 成熟雌性的两种主要菌株WT (HdrR) 和P53 (-/-) 的卵巢的影响。鱼被分配到对照组和三个UVA暴露组 (15 min，30 min和60 min/天)，持续三天，样品选择为暴露后24 h和14 d。与对照组相比，分析了暴露于UVA的鱼的组织学改变和卵母细胞闭锁百分比。改变包括厚度增加的高throphied滤泡细胞，绒毛膜破裂 (辐射带)，皮质肺泡受损以及细胞核和细胞质扭曲。野生型和p53缺陷鱼的闭锁百分比随UVA暴露剂量和时间的增加而显着增加。野生型的卵母细胞闭锁率明显高于p53突变体。这些结果表明，UVA暴露会引起p53和WT medaka卵母细胞的组织学改变，从而导致卵泡闭锁，从而降低女性的生殖能力和幼虫的产生。UVA卵母细胞反应显示出p53依赖性和独立的组织学改变，但是，在the鱼中，p53突变体对UVA的敏感性低于野生型。

BACKGROUND & AIMS: :Special high grade zinc and wrought zinc-aluminum (Zn-Al) alloys containing up to 5.5 wt % Al were processed, characterized, and implanted in rats in search of a new family of alloys with possible applications as bioabsorbable endovascular stents. These materials retained roll-induced texture with an anisotropic distribution of the second-phase Al precipitates following hot-rolling, and changes in lattice parameters were observed with respect to Al content. Mechanical properties for the alloys fell roughly in line with strength (190-240 MPa yield strength; 220-300 MPa ultimate tensile strength) and elongation (15-30%) benchmarks, and favorable elastic ranges (0.19-0.27%) were observed. Intergranular corrosion was observed during residence of Zn-Al alloys in the murine aorta, suggesting a different corrosion mechanism than that of pure zinc. This mode of failure needs to be avoided for stent applications because the intergranular corrosion caused cracking and fragmentation of the implants, although the composition of corrosion products was roughly identical between non- and Al-containing materials. In spite of differences in corrosion mechanisms, the cross-sectional reduction of metals in murine aorta was nearly identical at 30-40% and 40-50% after 4.5 and 6 months, respectively, for pure Zn and Zn-Al alloys. Histopathological analysis and evaluation of arterial tissue compatibility around Zn-Al alloys failed to identify areas of necrosis, though both chronic and acute inflammatory indications were present. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 245-258, 2018.

背景与目标： : 对含有高达5.5 wt % Al的特殊高级锌和锻造锌铝 (Zn-Al) 合金进行了加工，表征并植入大鼠中，以寻找可能用作生物可吸收血管内支架的新合金家族。这些材料在热轧后保留了辊诱导的织构，并具有第二相Al沉淀物的各向异性分布，并且观察到相对于Al含量的晶格参数变化。合金的机械性能与强度 (190-240 MPa的屈服强度; 220-300 MPa的极限拉伸强度) 和伸长率 (15-30%) 基准大致一致，并且观察到有利的弹性范围 (0.19-0.27%)。Zn-Al合金在鼠主动脉中停留期间观察到晶间腐蚀，表明腐蚀机理与纯锌不同。对于支架应用，需要避免这种失败模式，因为晶间腐蚀会导致植入物破裂和碎裂，尽管在不含铝的材料和含铝的材料之间腐蚀产物的成分大致相同。尽管腐蚀机理存在差异，但对于纯Zn和Zn-Al合金，在4.5个月和6个月后，鼠主动脉中金属的横截面还原在30-40% 和40-50% 几乎相同。尽管存在慢性和急性炎症指征，但组织病理学分析和Zn-Al合金周围动脉组织相容性评估未能确定坏死区域。©2017威利期刊公司J Biomed Mater Res B部分: 应用Biomater，106B: 245-258，2018。

BACKGROUND & AIMS: :In this study, we evaluated the effects of 10 wt% spherical silica filler (SSF) addition on 24-h compressive strength, modulus of elasticity, water uptake, and immediate setting shrinkage of conventional glass-ionomer (Fuji II and Experimental) and resin-modified glass-ionomer (Fuji II LC EM) cements. The glass-ionomer cement powders were modified by being mixed with 10 wt% SSFs with an average particle diameter of 0.3 microm. The materials were mixed to consistencies similar to the flow of Fuji II mixed with a powder-liquid ratio of 2.7:1 (w/w). The 24-h compressive strength, modulus of elasticity, water uptake, and immediate setting shrinkage were observed and the results compared with the original materials mixed with similar flow. The addition of SSF increased the compressive strength value to 1.1 times, while the increase of moduli of elasticity was 1.10 to 1.35 times. In general, the addition of SSF decreased the 24-h water uptake to 80-90% and reduced the immediate setting shrinkage to 70-79% of the original materials. The addition of 10 wt% SSF improved the characteristics of conventional and resin-modified glass-ionomer cement.

背景与目标： : 在这项研究中，我们评估了添加10 wt % 球形二氧化硅填料 (SSF) 对24小时抗压强度，弹性模量，吸水率，以及常规玻璃离聚物 (富士II和实验) 和树脂改性玻璃离聚物 (富士II LC EM) 水泥的立即固化收缩。通过与平均粒径为0.3微米的10 wt % SSFs混合来改性玻璃离聚物水泥粉末。将材料混合至类似于以2.7:1 (w/w) 的粉末-液体比混合的Fuji II的流动。观察了24小时的抗压强度，弹性模量，吸水率和立即凝固收缩率，并将结果与混合有相似流量的原始材料进行了比较。SSF的加入使抗压强度值增加到1.1倍，而弹性模量的增加1.10到1.35倍。通常，添加SSF将24小时的吸水率降低到原始材料的80-90%，并将立即凝结收缩率降低到70-79%。添加10 wt % SSF改善了常规和树脂改性的玻璃离聚物水泥的特性。

BACKGROUND & AIMS: :Here we investigate activation of the p53 pathway by inhibition of transcription. Comparison of cells with either mutant p53 or wt p53 indicated that inhibition of p53- dependent transcription is necessary and sufficient for wt p53 accumulation. In addition to Mdm-2, p21 is required for effective p53 degradation. Transient inhibition of transcription resulted in initial downregulation of p21 and Mdm-2 leading to accumulation of wt p53. This was followed by induction of p21 and Mdm-2, normalization of p53 levels, and p21-dependent growth arrest. Although simultaneous induction of p53 and p21 could be detected by immunoblot, levels of p53 and p21 were discordant in individual cells. By inducing p21 and Mdm-2, p53 discriminates between transient and sustained inhibition of transcription. Transient inhibition results in p21-dependent growth, while sustained inhibition of transcription leads to p53-facilitated cell death. One can envision p53 as a physiological sensor of transcriptional integrity. Transient inhibition of p53- stimulated transcription by numerous stimuli including nucleotide depletion, hypoxia, UV light may be an prevalent mechanism of activation of wt p53 and its downstream pathways.

背景与目标： : 在这里，我们研究通过抑制转录激活p53途径。与突变型p53或wt p53的细胞比较表明，抑制p53依赖性转录对于wt p53的积累是必要且足够的。除Mdm-2外，p21是有效的p53降解所必需的。转录的瞬时抑制导致p21和Mdm-2的初始下调，导致wt p53的积累。随后是p21和Mdm-2的诱导，p53水平的正常化以及p21-dependent的生长停滞。尽管可以通过免疫印迹检测到p53和p21的同时诱导，但单个细胞中p53和p21的水平不一致。通过诱导p21和Mdm-2，p53区分转录的瞬时和持续抑制。瞬时抑制导致p21-dependent生长，而持续抑制转录导致p53-facilitated细胞死亡。人们可以设想p53作为转录完整性的生理传感器。许多刺激 (包括核苷酸耗竭，缺氧，紫外线) 对p53刺激的转录的瞬时抑制可能是wt p53及其下游途径激活的普遍机制。