小老鼠摘果子

从前，在一片茂密的森林里，住着三只可爱的小老鼠：花花、妮妮、美美。

小老鼠的节日

靓讲堂：一个充（chōng）满童心童趣的童话，真可爱!原来，小老鼠也有自己的节日，也可以得到大家的喜爱和祝福啊。对呀，为什么不能呢？

小老鼠的信

咚咚!咚咚咚!有人在敲门，小老鼠打开门一看，原来是一封信。小老鼠一看，信上写着：“你好，小老鼠，我是猫大哥，你的妈妈被我给屹了。今天是清明节，为表示歉意，我和你一起去给她扫墓吧。”

小老鼠当作家

嗨！大家好，我是一只小老鼠，我叫多多，最近我一直在想怎么才可以让所有的老鼠们记住我。 做什么呢？正当我看着电视时，突然看见了一位作家正在签售卖书。“噢！我知道干什么了，我要当一名作家，当作家看上去真容易!”我想道。

小老鼠和铅笔

沃瓦的桌子上放着一支铅笔。一天，在他睡觉的时候，一只小老鼠偷偷摸摸地蹿到桌子上，见到铅笔，就用嘴叼住，往自己的洞穴里拖。

小老鼠救狮王

在一片很大的森林里．有一只狮子，它是这里的狮王。

小老鼠的魔法书

小老鼠有一本魔法书。那是一本可大可小的书，小老鼠可以把它装在口袋里，不管他是到外面去找吃的，还是散步、晒太阳，都能带着它，什么时候想看了，就可以掏出来看。如果正巧下雨了，那本书就能变大，变成一间人字形房子，硬壳的书皮变成屋顶和房檐，让小老鼠住在里面。

《小老鼠忙碌的一天》

《小老鼠忙碌的一天》是一个美丽又充满温情的故事。书里写了两只老鼠，大老鼠始终都在忙个不停：忙着翻土，忙着除草……而小老鼠呢，似乎始终都在淘气：悠闲地荡秋千，躺在车里望着天空发呆……

有效提问 点亮精彩课堂——以《小老鼠运大蛋》语言活动教学为例

我国著名教育家陶行知先生说：＂发明千千万,起点是一问。禽兽不如人,过在不会问。智者问得巧,愚者问得笨。＂诚然,学起于思,思源于疑。提问是一种教育智慧、一种教学艺术,也是教学过程中的一个重要环节,更是提高教学质量的有效手段。教师在设计问题时要做到由易到难,由浅入深,层层推进,从幼儿的认知水平出发,将提问的＂坡度＂转向提问的＂难度＂,这样的课堂提问才能够促进幼儿的发展,使课堂教学精彩纷呈。

Titanium dioxide induced inflammation in the small intestine

AIM:To investigate the effects of titanium dioxide (TiO2) nanoparticles (NPTiO 2 ) and microparticles (MPTiO 2 ) on the inflammatory response in the small intestine of mice. METHODS: Bl 57/6 male mice received distilled water suspensions containing TiO 2 (100 mg/kg body weight) as NPTiO 2 (66 nm), or MPTiO 2 (260 nm) by gavage for 10 d, once a day; the control group received only distilled water. At the end of the treatment the duodenum, jejunum and ileum were extracted for assessment of cytokines, inflammatory cells and titanium content. The cytokines interleukin (IL)-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-23, tumor necrosis factor-α (TNF-α), intracellular interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) were evaluated by enzyme-linked immunosorbent assay in segments of jejunum and ileum (mucosa and underlying muscular tissue). CD4 + and CD8 + T cells, natural killer cells, and dendritic cells were evaluated in duodenum, jejunum and ileum samples fixed in 10% formalin by immuno-histochemistry. The titanium content was determined by inductively coupled plasma atomic emission spectrometry. RESULTS: We found increased levels of T CD4 + cells (cells/mm 2 ) in duodenum:NP 1240 ± 139.4, MP 1070 ± 154.7 vs 458 ± 50.39 (P < 0.01); jejunum:NP 908.4 ± 130.3, MP 813.8 ± 103.8 vs 526.6 ± 61.43 (P < 0.05); and ileum:NP 818.60 ± 123.0, MP 640.1 ± 32.75 vs 466.9 ± 22.4 (P < 0.05). In comparison to the control group, the groups receiving TiO 2 showed a statistically significant increase in the levels of the inflammatory cytokines IL-12, IL-4, IL-23, TNF-α, IFN-γ and TGF-β. The cytokine production was more pronounced in the ileum (mean ± SE):IL-12: NP 33.98 ± 11.76, MP 74.11 ± 25.65 vs 19.06 ± 3.92 (P < 0.05); IL-4: NP 17.36 ± 9.96, MP 22.94 ± 7.47 vs 2.19 ± 0.65 (P < 0.05); IL-23: NP 157.20 ± 75.80, MP 134.50 ± 38.31 vs 22.34 ± 5.81 (P < 0.05); TNFα: NP 3.71 ± 1.33, MP 5.44 ± 1.67 vs 0.99± 019 (P < 0.05); IFNγ: NP 15.85 ± 9.99, MP 34.08 ± 11.44 vs 2.81 ± 0.69 (P < 0.05); and TGF-β: NP 780.70 ± 318.50, MP 1409.00 ± 502.20 vs 205.50 ± 63.93 (P < 0.05). CONCLUSION:Our findings indicate that TiO2 particles induce a Th1-mediated inflammatory response in the small bowel in mice.

Effect of vitamin E on oxidative stress status in small intestine of diabetic rat

AIM:To investigate the effect of vitamin E on oxidative stress status in the small intestine of diabetic rats. METHODS:Twenty-four male Wistar rats were randomly divided into three groups:Control (C),non-treated diabetic (NTD) and vitamin E-treated diabetic (VETD) groups. The increases in lipid peroxidation,protein oxidation and superoxide dismutase (SOD) in these three groups was compared after 6 wk. RESULTS:There was no significant difference in catalase activity between NTD and control rats. Compared to NTD rats,the treatment with vitamin E significantly decreased lipid peroxidation and protein oxidation,and also increased catalase activity and SOD. CONCLUSION:The results revealed the occurrence of oxidative stress in the small intestine of diabetic rats. Vitamin E,as an antioxidant,attenuates lipid peroxidation and protein oxidation,and increases antioxidant defense mechanism.

Expression of tissue inhibitor of matrix metalloproteinases-1 during aging in rat liver

AIM: To investigate the expression and role of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) during natural aging in rat liver and to detect the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. METHODS: The rats were divided into 3-mo-old group (n=5), 10-mo-old group (n=5) and 24-mo-old group (n=5). Histopathologic changes of liver were observed with HE and Masson stain. The location and protein expressions of TIMP-1 were determined by immunohistochemistry and Western blot; message RNA (mRNA) levels were measured in livers from rats of various ages by semi-quantitative reverse transcriptional polymerase chain reaction (RT PCR). In addition, the expression of MMP-2 and MMP-9 was assessed by RT-PCR and Western blot. RESULTS: Histologic examination showed that the aging liver had excessive fatty degeneration and collagen deposition. Immunohistochemical staining showed that TIMP-1 related antigen in livers was located in cytoplasm. The protein expression of TTMP-1 was significantly higher in the oldest animals and the mRNA expression was increased significantly in the 24-mo-old rats (t= 4.61, P= 0.002<0.05, 24-vs 10-mo-old rats; t=4.31, P=0.003<0.05, 24- vs 3-mo-old rats). The expression of MMP-2 and MMP-9 had no change during aging; the ratios TIMP-1/MMP-2 and TIMP-1/MMP-9 in aging liver were significantly higher than those in maturation and young livers. CONCLUSION: TIMP-1 may play an important role in the process of liver aging.

Composition and immuno-stimulatory properties of extracellular DNA from mouse gut flora

AIM To demonstrate that specific bacteria might release bacterial extracellular DNA(e DNA) to exert immunomodulatory functions in the mouse small intestine.METHODS Extracellular DNA was extracted using phosphate buffered saline with 0.5 mmol/L dithiothreitol combined with two phenol extractions. TOTO-1 iodide, a cell-impermeant and high-affinity nucleic acid stain, was used to confirm the existence of e DNA in the mucus layers of the small intestineand colon in healthy Male C57 BL/6 mice. Composition difference of e DNA and intracellular DNA(i DNA) of the small intestinal mucus was studied by Illumina sequencing and terminal restriction fragment length polymorphism(T-RFLP). Stimulation of cytokine production by e DNA was studied in RAW264.7 cells in vitro.RESULTS TOTO-1 iodide staining confirmed existence of e DNA in loose mucus layer of the mouse colon and thin surface mucus layer of the small intestine. Illumina sequencing analysis and T-RFLP revealed that the composition of the e DNA in the small intestinal mucus was significantly different from that of the i DNA of the small intestinal mucus bacteria. Illumina Miseq sequencing showed that the e DNA sequences came mainly from Gram-negative bacteria of Bacteroidales S24-7. By contrast, predominant bacteria of the small intestinal flora comprised Grampositive bacteria. Both e DNA and i DNA were added to native or lipopolysaccharide-stimulated Raw267.4 macrophages, respectively. The e DNA induced significantly lower tumor necrosis factor-α/interleukin-10(IL-10) and IL-6/IL-10 ratios than i DNA, suggesting the predominance for maintaining immune homeostasis of the gut.CONCLUSION Our results indicated that degraded bacterial genomic DNA was mainly released by Gram-negative bacteria, especially Bacteroidales-S24-7 and Stenotrophomonas genus in gut mucus of mice. They decreased pro-inflammatory activity compared to total gut flora genomic DNA.

Differences in neuroplasticity after spinal cord injury in varying animal models and humans

Rats have been the primary model to study the process and underlying mechanisms of recovery after spinal cord injury. Two weeks after a severe spinal cord contusion, rats can regain weight-bearing abilities without therapeutic interventions, as assessed by the Basso, Beattie and Bresnahan locomotor scale. However, many human patients suffer from permanent loss of motor function following spinal cord injury. While rats are the most understood animal model, major differences in sensorimotor pathways between quadrupeds and bipeds need to be considered. Understanding the major differences between the sensorimotor pathways of rats, non-human primates, and humans is a start to improving targets for treatments of human spinal cord injury. This review will discuss the neuroplasticity of the brain and spinal cord after spinal cord injury in rats, non-human primates, and humans. A brief overview of emerging interventions to induce plasticity in humans with spinal cord injury will also be discussed.

Gene expression profile in rat small intestinal allografts after cold preservation/reperfusion

AIM: To determine the changes of gene expression profile in small intestinal allografts in rats after cold preservation/ reperfusion, and to identify the genes relevant to cold preservation/reperfusion injury. METHODS: Heterotopic segmental small bowel transplantation was performed in six rats with a sham operation and they were used as controls. Total RNA was extracted from the allografts (experimental group) and normal intestines (control group) 1 h after cold preservation/ reperfusion, and then purified to mRNA, which was then reversely transcribed to cDNA, and labeled with fluorescent Cy5-dUTP and Cy3-dUTP to prepare hybridization probes. The mixed probes were hybridized to the cDNA microarray. After high-stringent washing, the fluorescent signals on cDNA microarray chip were scanned and analyzed. RESULTS: Among the 4 096 target genes, 82 differentially expressed genes were identified between the two groups. There were 18 novel genes, 33 expression sequence tags, and 31 previously reported genes. The selected genes may be divided into four classes: genes modulating cellular adhesion, genes regulating cellular energy, glucose and protein metabolism, early response genes and other genes. CONCLUSION: A total of 82 genes that may be relevant to cold preservation/reperfusion injury in small intestinal allografts are identified. Abnormal adhesion between polymorphonuclears and endothelia and failure in energy, glucose and protein metabolism of the grafts may contribute to preservation/reperfusion injury. The functions of the novel genes identified in our study need to be clarified further.

Effect of Buyang Huanwu Decoction on Platelet Activating Factor Content in Arterial Blood Preand Post-Arterial Thrombosis in Rats

To explore the effect of Buyang Huanwu Decoction (BHD) on platelet activating factor (PAF) content in arterial blood pre- and post-arterial thrombosis in rats, male Wistar rats were randomly divided into 3 groups, the medicine group treated with BHD, the control group with dexamethasone liquid, and the blank group with distilled water. Oral administration was given for 14 consecutive days, once daily. Model of arterial thrombosis was established in the animals 2 hours after final medication, the blood content of PAF, dry weight (DW) and occlusion time (OT) of thrombus, and dry weight of thrombus/body weight (TW/BW) ratio were observed. Results indicated that BHD could markedly lower the arterial blood content of PAF after thrombosis, increase the OT of thrombus, reduce the dry weight of thrombus and the TW/BW ratio (P

Physiological Testosterone Retards Cardiomyocyte Aging in Tfm Mice via Androgen Receptor-independent Pathway

Objective To determine whether testosterone modulates markers of cardiomyocytes aging via its classic androgen receptor （AR）-dependent pathway or conversion to estradiol. Methods Male littermates and testicular feminized （Tfm） mice were randomly separated into 4 experimental groups： littermate controls （n=8）, Tfm mice （n=7）, testosterone-treated Tfm mice （n=8） and Tfm mice treated with testosterone in combination with the aromatase inhibitor anastrazole （n=7）. Cardiomyocytes were isolated from mouse left ventricles, the activity of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px）, and the amount of malondialdehyde （MDA） were measured us- ing colorimetry method, and expression of p l 6~NKga and retinoblastoma （Rb） proteins were detected by Western blotting. Results The SOD and GSH-Px enzyme activities of cardiomyocytes were decreased, and the MDA levels and the expression of p l 6INK＊a and Rb proteins were increased in Tfm mice compared with control mice. An increase was observed in the activities of SOD and GSH-Px enzyme as well as a decrease in MDA levels and the expression of p 16~NK4a and Rb proteins in the testosterone-treated Tfm mice. After co-treatment with anastrazole in Tfm mice, these improvement were partly inhib- ited. Conclusion Physiological testosterone replacement can delay cardiomyocyte aging in Tfm mice, an effect that is independent of the AR pathway and in part conversion to estradiol.

Comparative study of histopathology changes between the PS1/APP double transgenic mouse model and Aβ_(1-40)-injected rat model of Alzheimer disease

Objective To identify the genetype of the PS1/APP double transgenie mouse model, then to analyse the histopathological changes in the brain and compare the differences between the transgenie mice models and Aβ1-40-injeeted rats models of Alzheimer disease. Methods The modified congo red staining, Nissl＇s staining and immunohistology staining was used to observe the Aβ deposits, activation of astrocyte respectively. Results ①The PS1/APP transgenic mouse extensively displayed Aβ deposits in the cortex and hippocampal structures, and GFAP positive cells were aggregated in mass and surrounded the congo red-positive plaque. ②The Aβ1-40-intrahippocmnpal-injeeted rat model showed the Aβ plaque deposits in the dentate gyrus of the hippocampus, with the astrocyte surrounded. The neurons loss was significant in the injection point and pin hole of injection with Nissl＇s staining methods. GFAP-positive cells increased significantly compared with the uninjected lateral of the hippocampus. Conclusion Although Aβ1-40-injected rat models could simulate some characteristic pathological features of human Alzheimer diseases, Aβ deposits and neurons loss in partial hippocampal, it would not simulate the progressive degenenration in the brain of AD. The double transgenie PS1/APP mice could simulate the specific pathogenesis and progressive changes of AD, mainly is Aβ deposits and the spongiocyte response , while no neurons loss were observed in this model.

给孩子一个有童话的艺术课堂

《小老鼠，上灯台》我先后在三个平行班上这一内容，因为教学思路的变化，教学效果迥异。