T cells promote the regeneration of neural precursor cells in the hippocampus of Alzheimer's disease mice

Alzheimer＇s disease is closely associated with disorders of neurogenesis in the brain, and growing evidence supports the involvement of immunological mechanisms in the development of the disease. However, at present, the role of T cells in neuronal regeneration in the brain is unknown. We injected amyloid-beta 1-42 peptide into the hippocampus of six BALB/c wild-type mice and six BALB/c-nude mice with T-cell immunodeficiency to establish an animal model of Alzhei- mer＇s disease. A further six mice of each genotype were injected with same volume of normal saline. Immunohistochemistry revealed that the number of regenerated neural progenitor cells in the hippocampus of BALB/c wild-type mice was significantly higher than that in BALB/c-nude mice. Quantitative fluorescence PCR assay showed that the expression levels of peripheral T cell-associated cytokines （interleukin-2, interferon-y） and hippocampal microglia-related cyto- kines （interleukin-113, tumor necrosis factor-a） correlated with the number of regenerated neural progenitor cells in the hippocampus. These results indicate that T cells promote hippocampal neurogenesis in Alzheimer＇s disease and T-cell immunodeficiency restricts neuronal regeneration in the hippocampus. The mechanism underlying the promotion of neuronal regeneration by T cells is mediated by an increased expression of peripheral T cells and central microglial cytokines in Alzheimer＇s disease mice. Our findings provide an experimental basis for understanding the role of T cells in Alzheimer＇s disease.

Toxic effect of acrylamide on the development of hippocampal neurons of weaning rats

Although numerous studies have examined the neurotoxicity of acrylamide in adult animals,the effects on neuronal development in the embryonic and lactational periods are largely unknown.Thus,we examined the toxicity of acrylamide on neuronal development in the hippocampus of fetal rats during pregnancy.Sprague-Dawley rats were mated with male rats at a 1：1 ratio.Rats were administered 0,5,10 or 20 mg/kg acrylamide intragastrically from embryonic days 6–21.The gait scores were examined in pregnant rats in each group to analyze maternal toxicity.Eight weaning rats from each group were also euthanized on postnatal day 21 for follow-up studies.Nissl staining was used to observe histological change in the hippocampus.Immunohistochemistry was conducted to observe the condition of neurites,including dendrites and axons.Western blot assay was used to measure the expression levels of the specific nerve axon membrane protein,growth associated protein 43,and the presynaptic vesicle membrane specific protein,synaptophysin.The gait scores of gravid rats significantly increased,suggesting that acrylamide induced maternal motor dysfunction.The number of neurons,as well as expression of growth associated protein 43 and synaptophysin,was reduced with increasing acrylamide dose in postnatal day 21 weaning rats.These data suggest that acrylamide exerts dose-dependent toxic effects on the growth and development of hippocampal neurons of weaning rats.

Analysis of the injection layer of PTCDA in OLEDs using x-ray photoemission spectroscopy and atomic force microscopy

Through the investigation of the sample surface and interface of 3, 4, 9, 10-perylenetetracarboxylic dianhydride （PTCDA）/indium-tin-oxide （ITO） thin films using atomic force microscopy, it has been found that the surface is complanate, the growth is uniform and the defects cover basically the surface of ITO. Furthermore, the number of pinholes is small. The analysis of the sample surface and interface further verifies this result by using x-ray photoemission spectroscopy. At the same time, PTCDA is found to have the ability of restraining the diffusion of chemical constituents from ITO to the hole transport layer, which is beneficial to the improvement of the performance and the useful lifetime of the organic light emitting diodes （OLEDs）.

Influence of flavone extract from cultivated saussurea on learning and memory in a mouse model of Alzheimer's disease A comparison with estradiol benzoate

The present study established a mouse model of Alzheimer＇s disease, and investigated the effects of treatment with flavone extract from artificially cultivated saussurea. A positive control group was treated with estradiol benzoate, and learning and memory ability were examined in the 8-arm radial maze. The learning and recognition ability of mice with Alzheimer＇s disease treated with flavone extract was significantly improved and the number of hippocampal neurons was significantly increased in the flavone-treated and positive control groups compared with the model group. The results indicate that flavone extract from artificially cultivated saussurea can improve learning and memory deficits in mice with Alzheimer＇s disease, exerting effects similar to those of estradiol benzoate.

Synthesis,DNA-binding,cytotoxicity and cleavage studies of unsymmetrical oxovanadium complexes

An unsymmetrical oxovanadium complex [VO(SAA)(phen) ](1),(SAA = salicylidene anthranilic acid,phen = phenanthroline) and its novel derivatives [VO(MOSAA)(phen) ](2)(MOSAA = 2-hydroxy-4-methoxysalicylidene anthranilic) have been synthesized and characterized by elemental analysis,UV-Vis,ES-MS,IR and 1 H NMR.The interaction of these two complexes with CT-DNA was investigated by absorption titration,fluorescence spectra,viscosity measurements and thermal denaturation.Their photocleavage reactions with pBR322 supercoiled plasmid DNA were investigated by gel electrophoresis experiments.The cytotoxicity of these two complexes against Myeloma cell(Ag8.653) and Gliomas cell(U251) have been assessed by MTT assay.The experimental results show that both complexes 1 and 2 bind to CT-DNA in classical intercalation mode,and the DNA-binding affinity of the complex 1 is larger than that of complex 2.It is interesting to note that these two complexes prominently enhance the oxidative cleavage of supercoiled pBR322 DNA and both complexes present cytotoxic activities against Ag8.653 and U251 cell lines.Complex 1 possessed the more potent inhibitory effect against the two cell lines of the two complexes.

Growth Mode Investigation of 3,4,9,10-perylenetetra-carboxylic Dianhydride on p-Si Substrates by X-ray Photoemission Spectroscopy

The growth mode of 3,4,9,10-perylenetetra-carboxylic dianhydride(PTCDA) deposited on p-Si substrates can be deduced by X-ray Photoemission Spectroscopy(XPS). The spectrum and fine spectrum at the surface of specimen are studied. Firstly, PTCDA molecules assemble at the defects to form lots of three-dimensional island-like PTCDA crystal nucleuses, and then by the action of delocalized big π bond, two adjacent layers of PTCDA molecules overlap to some extent and finally island-like structure forms. PTCDA molecules of benzene ring combine with Si atoms at the defects, and that of acid anhydride radicals combine with Si atoms at the perfect fraction of the surface. In the course of combination, although the structure of benzene ring doesn't change, the chemical reaction of acid anhydride radicals and Si occurs to break off C=O bond in acid anhydride, and then C-Si-O and silicon oxide might be produced.

Photocleavage Properties and DNA-Binding Studies of Oxovanadium Complexes Incorporating 2-(2-Hydroxybenzylideneamino) Isoindoline-1,3-Dione and Fluoro-Phenanthroline Derivatives

Three mononuclear oxovanadium complexes [VO(Hbid)(CF3PIP)] (1) (Hbid=(E)-2-(2-hydroxybenzylideneamino) isoindoline-1,3-dione, CF3PIP=2-(2-trifluoromethyl phenyl)imidazole[4,5-f][1,10] phenanthroline), [VO(Hbid)(m-CF3PIP)];(2) (m-CF3PIP=2-(3-trifluoromethyl phenyl)imidazole [4, 5-f][1,10]phenanthroline) and [VO(Hbid)(p-CF3PIP)];(3) (p-CF3PIP=2-(4-trifluoromethyl phenyl) imidazole[4,5-f][1,10]phenanthroline) have been synthesized and characterized by elemental analysis, IR, molar conductance, ES-MS and 1H NMR. The DNA-binding properties of these complexes were studied by using UV-Vis absorption titration, fluorescence spectra, viscosity measurements and thermal denaturation studies. The results show that 1, 2 and 3 interact with calf thymus DNA (CT-DNA) by intercalation modes and the magnitude of their intrinsic binding constants (Kb values) follows the order: 2 < 1 < 3. Furthermore, their photocleavage properties with pBR322 plasmid DNA were investigated by agarose gel electrophoresis experiments. The DNA cleavage capacity of complex 3 is also stronger than that of 1 and 2.

Homological Dimension of Crossed Products of Hopf Algebras

Let H be a finite dimensional cocommutative Hopf algebra and A an H-module algebra. In this paper, we characterize the projectivity (injectivity) of M as a left A#σH-module when it is projective (injective) as a left A-module. The sufficient and necessary condition for A#σH, the crossed product, to have finite global homological dimension is given, in terms of the global homological dimension of A and the surjectivity of trace maps, provided that H is cocommutative and A is commutative.

Inhibitory Effect of α-Pinene on SGC-7901 Cell Proliferation and the Mechanism of ATM Kinase Signaling Pathway

Objective: To research the inhibitory effect on SGC-7901 cells of α-pinene, and the related mechanism of α-pinene. Methods: Used the MTT method to detect inhibition rate and western blotting to detect the influence on expression of ATM, Phos-S1981ATM, H2AX, γH2AX, CHK2 and p-CHK2, p53 and phos-p53 cell cycle related protein in SGC-7901 cells. Results: The research found α-pinene could inhibit the proliferation of SGC-7901 cells observably in vitro, and the inhibition rate assumes the dependence on concentration;and western blotting results showed that, α-pinene could activate phospho-ATM, increase the amount of γH2AX (p p < 0.05);increase the expression of p-CHK2, p53 and phos-p53 (p p p < 0.05);But there is no significant effect on expression of CHK2 (p > 0.05). Conclusions: α-pinene could inhibit the proliferation of SGC-7901 cells, and by inducing ATM (Ataxia Telangiectasia-Mutated) kinase signal pathway in DNA damage response, activating cell cycle checkpoint, making the cell cycle arrest then exerts its anti-tumor effects.

Differential expression of immune-related genes between healthy volunteers and type 2 diabetic patients with spleen-deficiency pattern

OBJECTIVE: To investigate the clinical differentiation of spleen-deficiency pattern(SDP), a group of symptoms and signs defined in terms of Traditional Chinese Medicine for its clinical practice.METHODS: Peripheral venous blood(> 3 m L) was collected from each of six type 2 diabetes mellitus(T2DM)-SDP patients and six healthy volunteers. After the isolation of peripheral white blood cells(PWBCs), total RNA was extracted, and quality control was performed on all RNA samples. Microarray experiments were conducted using the Agilent human whole genome gene chip, and genes demonstrating differential expression were screened. Bioinformatics analysis was conducted on these genes using several online databases.RESULTS: We screened a total of 175 differentially expressed genes(DEGs), of which 111(63%) were down-regulated and 64(37%) were up-regulated in T2DM-SDP patients compared with healthy controls. Among the 175 genes, 158 had biological function annotations: 46(29%) were directly related to an individual's immune regulation or response, 25(16%) were associated with substance and energy metabolism of PWBCs which could also indirectly influence immunity, and the remaining87(55%) were involved in a variety of PWBC biological processes that might eventually influence the immune function. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the DEGs were predominantly enriched in seven immune-related pathways. Hierarchical cluster analysis identified gene expression patterns that were distinguishable between the two study groups.CONCLUSION: Our results suggest that T2DM-SDP patients experience significant hypoimmunity and/or immune dysfunctions, and possess a specific gene expression profile. These findings offer new insights into SDP and the clinical pattern differentiation of T2DM-SDP.

Comparative evaluation of the physicochemical properties of nano-hydroxyapatite/collagen and natural bone ceramic/collagen scaffolds and their osteogenesis-promoting effect on MC3T3-E1 cells

The use of various types of calcium phosphate has been reported in the preparation of repairing materials for bone defects.However,the physicochemical and biological properties among them might be vastly different.In this study,we prepared two types of calcium phosphates,nano-hydroxyapatite(nHA)and natural bone ceramic(NBC),into 3D scaffolds by mixing with type I collagen(CoL),resulting in the nHA/CoL and NBC/CoL scaffolds.We then evaluated and compared the physicochemical and biological properties of these two calcium phosphates and their composite scaffold with CoL.Scanning electron microscopy(SEM),X-ray photoelectron spectroscopy(XPS),Fourier-transform infrared spectroscopy(FTIR),X-ray diffraction spectroscopy(XRD)and compressive tests were used to,respectively,characterize the morphology,composition,distribution and the effect of nHA and NBC to collagen.Next,we examined the biological properties of the scaffolds using cytotoxicity testing,flow cytometry,immunofluorescence staining,biocompatibility testing,CCK-8 assays and RT-PCR.The results reflected that the Ca2t released from nHA and NBC could bind chemically with collagen and affect its physicochemical properties,including the infrared absorption spectrum and compression modulus,among others.Furthermore,the two kinds of scaffolds could promote the expression of osteo-relative genes,but showed different gene induction properties.In short,NBC/CoL could promote the expression of early osteogenic genes,while nHA/CoL could upregulate late osteogenic genes.Conclusively,these two composite scaffolds could provide MC3T3-E1 cells with a biomimetic surface for adhesion,proliferation and the formation of mineralized extracellular matrices.Moreover,nHA/CoL and NBC/CoL had different effects on the period and extent ofMC3T3-E1 cell mineralization.

Identification of microRNA and analysis of target genes in Panax ginseng

Objective: Ginsenosides, polysaccharides and phenols, the main active ingredients in Panax ginseng, are not different significantly in content between 3 and 5 years old of ginsengs called Yuan ginseng and more than ten years old ones called Shizhu ginseng. The responsible chemical compounds cannot fully explain difference in efficacy between them. According to reports in Lonicerae Japonicae Flos(Jinyinhua in Chinese) and Glycyrrhizae Radix et Rhizoma(Gancao in Chinese), microRNA may play a role in efficacy,so we identified microRNAs in P. ginseng at the different growth years and analyzed their target genes.Methods: Using high-throughput sequencing, the RNA-Seq, small RNA-Seq and degradome databases of P. ginseng were constructed. The differentially expressed microRNAs was identified by qRT-PCR.Results: A total of 63,875 unigenes and 24,154,579 small RNA clean reads were obtained from the roots of P. ginseng. From these small RNAs, 71 miRNA families were identified by bioinformatics target prediction software, including 34 conserved miRNAs, 37 non-conserved miRNA families, as well as 179 target genes of 17 known miRNAs. Through degradome sequencing and computation, we finally verified 13 targets of eight miRNAs involved in transcription, energy metabolism, biological stress and disease resistance, suggesting the significance of miRNAs in the development of P. ginseng. Consistently, major miRNA targets exhibited tissue specificity and complexity in expression patterns.Conclusion: Differential expression microRNAs were found in different growth years of ginsengs(Shizhu ginseng and Yuan ginseng), and the regulatory roles and functional annotations of miRNA targets in P. ginseng need further investigation.

Extraction and verification of miRNA from ginseng decoction

Objective: To verify the existence of microRNAs(miRNAs) extracted from fresh ginseng decoction.Methods: Fresh ginseng was prepared into decoction according to the conventional method. The miRNA were extracted from the condensed ginseng decoction by plant microRNA extraction kit. Then miRNA were treated by DNase I and subjected to agarose gel electrophoresis and Agilent 2100 bioanalysis. Mi R-159 and mi R-6135, which were highly expressed in ginseng, were selected and verified by real-time quantitative PCR to detect the expression in the decoction.Results: Ginseng miRNA were successfully extracted from fresh decoction. Mi R-159 and mi R-6135 were expressed in fresh decoction with lower levels than those of fresh ginseng.Conclusion: miRNAs stably existed after processing, and retained some stability after high-temperature treatment. The findings provide a valuables basis for the further studies on ginseng miRNAs.

Influences of AMY1 gene copy number and protein expression on salivary alpha-amylase activity before and after citric acid stimulation in splenic asthenia children

OBjECTIVE:To compare the correlations between salivary alpha-amylase(sAA) activity and amylase,alpha 1(salivary) gene(AMY1) copy number or its gene expression between splenic asthenia and healthy children,and investigate the reasons of attenuated sAA activity ratio before and after citric acid stimulation in splenic asthenia children.METHODS:Saliva samples from 20 splenic asthenia children and 29 healthy children were collected before and after citric acid stimulation.AMY1 copy number,sAA activity,and total sAA and glycosylated sAA contents were determined,and their correlations were analyzed.RESULTS:Although splenic asthenia and healthy children had no differences in AMY1 copy number,splenic asthenia children had positive correlations between AMY1 copy number and sAA activity before or after citric acid stimulation.Splenic asthenia children had a higher sAA glycosylated proportion ratio and glycosylated sAA content ratio,while their total sAA content ratio and sAA activity ratio were lower compared with healthy children.The glycosylated sAA content ratio was higher than the total sAA content ratio in both groups.Splenic asthenia and healthy children had positive correlations between total sAA or glycosylated sAA content and sAA activity.However,the role played by glycosylated sAA content in sAA activity in healthy children increased after citric acid stimulation,while it decreased in splenic asthenia children.CONCLUSION:Genetic factors like AMY1 copy number variations,and more importantly,sAA glycosylation abnormalities leading to attenuated sAA activity after citric acid stimulation,which were the main reasons of the attenuated sAA activity ratio in splenic asthenia children compared with healthy children.

Exponential stability of a pendulum in dynamic boundary feedback with a viscous damped wave equation

In this paper,we continue the earlier work[Lu,L,&Wang,D.L.(2017).Dynamic boundary feed-back of a pendulum coupled with a viscous damped wave equation.In Proceedings of the 36th Chinese Control Conference(CCQ)(pp.1676-1680)]on study the stability of a pendulum coupled with a viscous damped wave equation model.This time we get the exponential stability result which is much better than the previous strong stability.By a detailed spectral analysis and opera-tor separation,we establish the Riesz basis property as well as the spectrum determined growth condition for the system.Finally,the exponential stability of the system is achieved.

Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer cell proliferation in vitro and in vivo

Midline2 （MID2） is an ubiquitin-conjugating E2 enzyme linked to tumor progression and a novel interacting partner of breast cancer 1, early-onset 0BRCA1）. However, the role of MID2 in breast cancer remains unknown. This study investigated the expression, prognostic value, and role of MID2 in breast cancer. The expression of MID2 mRNA and protein was significantly upregulated in breast cancer tissue and established cell lines compared with that in normal breast epithelial cells and paired adjacent non-tumor tissue （P 〈 0.001）. Immunohistochemical analysis demonstrated that MID2 was overexpressed in 272 of 284 （95.8%） paraffin- embedded, archived breast cancer tissue. Moreover, MID2 expression increased with advanced clinical stage （P 〈 0.001）. High MID2 expression was significantly associated with advanced clinical stages and T, N, and M staging （all P 〈 0.05）. Univariate and multivariate analyses indicated that high MID2 expression was an independent prognostic factor for poor overall survival in the entire cohort （93.73 vs. 172.1 months; P 〈 0.001, log- rank test） and in subgroups with stages Tis ＋ Ⅰ ＋ Ⅱ and Ⅲ ＋ Ⅳ. Furthermore, 3-（4,5-dimethyl-2-thiazolyl）-2,5- diphenyl-2H-tetrazolium bromide colony formation, and anchorage-independent growth ability assays were conducted. Results showed that siRNA silencing of MID2 expression significantly reduced MCF-7 and MDA-MB- 231 cell proliferation in vitro and blocked the growth of MDA-MB-231 cell xenograft tumors in vivo （P 〈 0.05）. This study indicated that MID2 may be a novel prognostic marker and interventional target in breast cancer.

Erratum to: Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer cell proliferation in vitro and in vivo

The immunohistochemistry(IHC)staining of MID2 in“ANT”from Patient 2 and“T”from Patient 6 in original Fig.2C(Page 45)should be corrected.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.