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Replacement of the sluggish anodic reaction in water electrocatalysis by a thermodynamically favorable urea oxidation reaction (UOR) offers the prospect of energy-saving H

Subjective cognitive decline (SCD) is a preclinical asymptomatic stage of Alzheimer’s disease (AD). Accurate diagnosis of SCD represents the greatest challenge for current clinical practice. The multimodal magnetic resonance imaging (MRI) features of 7 brain networks and 90 regions of interests from Chinese and ANDI cohorts were calculated. Machine learning (ML) methods based on support vector machine (SVM) were used to classify SCD plus and normal control. To assure the robustness of ML model, above analyses were repeated in amyloid β (Aβ) and apolipoprotein E (APOE) ɛ4 subgroups. We found that the accuracy of the proposed multimodal SVM method achieved 79.49% and 83.13%, respectively, in Chinese and ANDI cohorts for the diagnosis of the SCD plus individuals. Furthermore, adding Aβ pathology and ApoE ɛ4 genotype information can further improve the accuracy to 85.36% and 82.52%. More importantly, the classification model exhibited the robustness in the crossracial cohorts and different subgroups, which outperforms any single and 2 modalities. The study indicates that multimodal MRI imaging combining with ML classification method yields excellent and powerful performances at categorizing SCD due to AD, suggesting potential for clinical utility.

Exploring individual brain atrophy patterns is of great value in precision medicine for Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, the current individual brain atrophy detection models are deficient. Here, we proposed a framework called generative adversarial network constrained multiple loss autoencoder (GANCMLAE) for precisely depicting individual atrophy patterns. The GANCMLAE model was trained using normal controls (NCs) from the Alzheimer's Disease Neuroimaging Initiative cohort, and the Xuanwu cohort was employed to validate the robustness of the model. The potential of the model for identifying different atrophy patterns of MCI subtypes was also assessed. Furthermore, the clinical application potential of the GANCMLAE model was investigated. The results showed that the model can achieve good image reconstruction performance on the structural similarity index measure (0.929 ± 0.003), peak signal-to-noise ratio (31.04 ± 0.09), and mean squared error (0.0014 ± 0.0001) with less latent loss in the Xuanwu cohort. The individual atrophy patterns extracted from this model are more precise in reflecting the clinical symptoms of MCI subtypes. The individual atrophy patterns exhibit a better discriminative power in identifying patients with AD and MCI from NCs than those of the t-test model, with areas under the receiver operating characteristic curve of 0.867 (95%: 0.837-0.897) and 0.752 (95%: 0.71-0.790), respectively. Similar findings are also reported in the AD and MCI subgroups. In conclusion, the GANCMLAE model can serve as an effective tool for individualised atrophy detection.

Background. Subjective cognitive decline (SCD) is the earliest symptom stage of Alzheimer’s disease (AD). Previous studies have shown that the study setting is an important influence factor of SCD. However, the effect of this factor among a Chinese population with SCD is not clear. Here, we aim to compare the clinical characteristics of SCD between a convenience and a population-based sample in China. Methods. We included a convenience sample of 212 SCD subjects and a population-based sample of 110 SCD subjects. We performed univariate analysis to evaluate the between-group differences in sociodemographic characteristics, neuropsychological performance, psychiatric conditions, different cognitive domains, and the SCD-plus criteria. Multiple linear regression model was established, adjusted for sex, age, and education, and compared the neuropsychological performance between the groups. Results. The convenience sample had more years of education, a higher family history of dementia, and higher neuropsychological and anxiety depression score than the population-based sample. Using sex, age, education, group as the independent variables, and neuropsychological score as the dependent variable, multiple linear regression model was established; a statistically significant neuropsychological score difference (MoCA-B, AVLT-H-N4, AVLT-H-N5, AVLT-H-N7, AFT, and STT-B) was found between the two samples. In the SCD cognitive domains, the population-based sample had more complaints about declines in their language and planning domains. For SCD-plus criteria in memory domain, the convenience sample had more complaints, worry, and cognitive decline within the last 5 years, along with medical help-seeking. Conclusion. There were some different characteristics among SCD individuals between convenience samples and population-based samples in China.

Exploring highly efficient, robust, and stable catalysts for urea electrolysis is intensively desirable for hydrogen production but remains a challenging task. In this work, novel, well-aligned, self-supported NiS/Ni

The effects of oxygen nonstoichiometry on material formation, geometrical structure, and electronic structures together with carrier conductions of CaMnO3 perovskite are comprehensively studied in detail. Specifically, the formation energy of oxygen nonstoichiometry in CaMnO3 perovskite is 8.01 eV. It has formation enthalpy of −7.10 eV. The MnO6 octahedron is diminished along b and c, it is expanded along a. All Mn–O bindings tend to tilt and the MnO6 octahedron is distorted. The strength of Mn–O bindings parallel to the a–c plane is enhanced; the strength of Mn–O bindings parallel to the b direction is weakened. The band gaps are 0.804 eV and 0.065 eV for the CaMnO3 and CaMnO2.75, respectively. The work functions are 4.69 eV and 2.58 eV, respectively. The p orbital electrons form the upper valance bands and the d orbital electrons form the lower conduction bands. The Ca s, Mn d and O p electrons contribute to carrier conductions for CaMnO2.75 perovskite.

Background Plasma amyloid-β (Aβ) may facilitate identification of individuals with brain amyloidosis. Gut microbial dysbiosis in Alzheimer’s disease (AD) is increasingly being recognized. However, knowledge about alterations of gut microbiota in preclinical AD, as well as whether the combination of plasma Aβ and gut microbiota could identify preclinical AD, remains largely unknown. Methods This study recruited 34 Aβ-negative cognitively normal (CN−) participants, 32 Aβ-positive cognitively normal (CN+) participants, and 22 patients with cognitive impairment (CI), including 11 patients with mild cognitive impairment (MCI) and 11 AD dementia patients. All participants underwent neuropsychological assessments and fecal microbiota analysis through 16S ribosomal RNA (rRNA) Illumina Miseq sequencing technique. Meso Scale Discovery (MSD) kits were used to quantify the plasma Aβ40, Aβ42, and Aβ42/Aβ40 in CN− and CN+ participants. Using Spearman’s correlation analysis, the associations of global standard uptake value rate (SUVR) with altered gut microbiota and plasma Aβ markers were separately evaluated. Furthermore, the discriminative power of the combination of gut microbiota and plasma Aβ markers for identifying CN+ individuals was investigated. Results Compared with the CN− group, the CN+ group showed significantly reduced plasma Aβ42 (p = 0.011) and Aβ42/Aβ40 (p = 0.003). The relative abundance of phylum Bacteroidetes was significantly enriched, whereas phylum Firmicutes and class Deltaproteobacteria were significantly decreased in CN+ individuals in comparison with that in CN− individuals. Particularly, the relative abundance of phylum Firmicutes and its corresponding SCFA-producing bacteria exhibited a progressive decline tendency from CN− to CN+ and CI. Besides, the global brain Aβ burden was negatively associated with the plasma Aβ42/Aβ40 (r = −0.298, p = 0.015), family Desulfovibrionaceae (r = −0.331, p = 0.007), genus Bilophila (r = −0.247, p = 0.046), and genus Faecalibacterium (r = −0.291, p = 0.018) for all CN participants. Finally, the combination of plasma Aβ markers, altered gut microbiota, and cognitive performance reached a relatively good discriminative power in identifying individuals with CN+ from CN− (AUC = 0.869, 95% CI 0.782 ~ 0.955). Conclusions This study provided the evidence that the gut microbial composition was altered in preclinical AD. The combination of plasma Aβ and gut microbiota may serve as a non-invasive, cost-effective diagnostic tool for early AD screening. Targeting the gut microbiota may be a novel therapeutic strategy for AD. Trial registration This study has been registered in ClinicalTrials.gov (NCT03370744, https://www.clinicaltrials.gov) in November 15, 2017.

A robust algorithm in the form of a 3-D dynamic system is introduced to identify the frequency, the in-phase component, the orthogonal component, and the amplitude of a sinusoidal signal with unknown frequency. The condition for asymptotically convergent property of the dynamic system is analyzed sequentially by time scale change, variable transformation, slow integral manifold, averaging method, Lyapunov stability theorem, and stability theory of Mathieu equation. The robustness is embodied in two aspects: 1) the actual values of both frequency and amplitude slightly influence the convergent property and 2) two design parameters have independent effects on performance of both frequency identification and amplitude identification, respectively. Simulation results verify the validity.

We investigated the relationship between urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) levels and apolipoprotein epsilon 4 (ApoE ɛ4) alleles, as well as other factors that cause cognitive decline, in the cognitively normal population. We recruited 329 cognitively normal right-handed Han Chinese subjects who completed ApoE gene testing and urinary AD7c-NTP testing. There was no significant difference in urinary AD7c-NTP levels between the normal control and subjective cognitive decline groups. Urinary AD7c-NTP levels were significantly higher in subjects with ApoE ɛ3/4 and 4/4 [0.6074 (0.6541) ng/mL] than in subjects without ApoE ɛ4 [0.4368 (0.3392) ng/mL and 0.5287 (0.3656) ng/mL], and urinary AD7c-NTP levels positively correlated with ApoE genotype grade (r=0.165, p=0.003). There were significant differences in urinary AD7c-NTP levels between subjects with and without a history of coronary heart disease or diabetes. Urinary AD7c-NTP levels were not related to years of education, nature of work, family history of dementia, a history of hypertension, stroke, anemia, or thyroid dysfunction. Urinary AD7c-NTP levels were positively correlated with ApoE grade in the cognitively normal population. The relationship between risk factors of cognitive decline and urinary AD7c-NTP levels provides a new way for us to understand AD and urinary AD7c-NTP.

Background: Structural magnetic resonance imaging (MRI)-based visual rating scales are considered as the primary method for rapid and cost-effective evaluation of regional brain atrophy in patients with Alzheimer’s disease (AD) in routine clinical practice. Both medial temporal lobe atrophy (MTA) and posterior atrophy (PA) visual rating scales have been reported to be useful in AD diagnosis. However, very few existing studies have investigated the efficacy of combined MTA and PA for identification of amnestic mild cognitive impairment (aMCI) from cognitively normal elderly.Methods: This study included T1-weighted MRI images acquired inXuanwu Hospital of Capital Medical University, Beijing, China from two different cohorts. In the first cohort, we recruited 73 patients with aMCI and 48 group-matched cognitively normal controls for the training and validation. Visual assessments of MTA and PA, including left MTA, right MTA, mean MTA, left PA, right PA and mean PA, were carried out from each participant. Global gray matter (GM) volume and density was estimated using voxel-based morphometry analysis as the objective reference. Based on the receiver operating characteristic (ROC) analysis, we investigated the discriminative power of single visual rating scale and the combination of MTA and PA for successful classification between the two diagnostic groups, respectively, and then compared them to GM measures. The second cohort, consisted of 33 aMCI patients and 45 NCs, was used to verify the reliability of the discriminative power of visual assessments.Results: In the first cohort, visual rating scales of MTA and PA showed different potential to distinguish aMCI from controls. Moreover, the combination of MTA and PA exhibited the best discriminative power, with the AUC of 0.818 ± 0.041, which was similar to the diagnostic accuracy of GM volumetric measures (0.857 ± 0.034). The discriminative power was verified in the second cohort when combining MTA and PA visual rating scales, with the AUC of 0.824 ± 0.058.Conclusion: The combined visual rating scales of MTA and PA demonstrated practical diagnostic values for distinguishing aMCI patients from controls, suggesting its potential to serve as a convenient and reproducible method to assess the degree of atrophy in the clinical setting.

Background: Lipid emulsion has been identified as a potent rescuing agent for cardiac arrest caused by local anesthetic overdose. In this animal study, we investigated whether prophylactic infusion of emulsified isoflurane, a mixture of lipid emulsion and isoflurane, could increase the tolerability for bupivacaine-induced cardiac toxicity.Methods: Rats were randomly assigned to receive one of the following treatments: saline, 30% Intralipid, 4% Emulsified Isoflurane (4% EISO), 2% EISO, 0.5% propofol, 0.25% propofol, inhaled isoflurane plus 30% Intralipid, or inhaled isoflurane plus saline, for 15 minutes. Then 0.75% bupivacaine was infused at the rate of 8 ml/kg/min (n=10 in each group). The time needed to induce cardiac arrest was recorded and the bupivacaine dose was calculated. Another set of rats were intubated for mechanical ventilation and catheterized for invasive arterial pressure monitoring while receiving one of the following sedative pretreatments for 15 minutes: 4% EISO, 0.5% propofol, inhaled isoflurane plus saline, or inhaled isoflurane plus 30% Intralipid (n=10 in each group). Then bupivacaine was infused at the rate of 8 ml/kg/min for 120 seconds (sublethal dose). The hemodynamic parameters were recorded till circulation fully recovered.Results: Pretreatment with 4% EISO significantly increased the dose of bupivacaine required to induce cardiac arrest (68.69±7.57 mg/kg vs. 26.61±5.13 mg/kg for saline, P

// Xiao-Ni Wang 1,* , Yang Zeng 2,* , Guan-Qun Chen 1 , Yi-He Zhang 2 , Xuan-Yu Li 1 , Xu-Yang Hao 2 , Yang Yu 1 , Meng Zhang 2 , Can Sheng 1 , Yu-Xia Li 1 , Yu Sun 1 , Hong-Yan Li 1 , Yang Song 1 , Kun-Cheng Li 3 , Tian-Yi Yan 2 , Xiao-Ying Tang 2 and Ying Han 1,4 1 Department of Neurology, XuanWu Hospital of Capital Medical University, Beijing, China 2 School of Life Science, Beijing Institute of Technology, Beijing, China 3 Department of Radiology, XuanWu Hospital of Capital Medical University, Beijing, China 4 Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, Beijing, China * These authors have contributed equally to this work Correspondence to: Ying Han, email: // Xiao-Ying Tang, email: // Tian-Yi Yan, email: // Keywords : subjective cognitive decline, amnestic mild cognitive impairment, network, white matter, diffusion tensor imaging, Pathology Section Received : October 31, 2015 Accepted : June 29, 2016 Published : July 13, 2016 Abstract Network analysis has been widely used in studying Alzheimer’s disease (AD). However, how the white matter network changes in cognitive impaired patients with subjective cognitive decline (SCD) (a symptom emerging during early stage of AD) and amnestic mild cognitive impairment (aMCI) (a pre-dementia stage of AD) is still unclear. Here, structural networks were constructed respectively based on FA and FN for 36 normal controls, 21 SCD patients, and 33 aMCI patients by diffusion tensor imaging and graph theory. Significantly lower efficiency was found in aMCI patients than normal controls (NC). Though not significant, the values in those with SCD were intermediate between aMCI and NC. In addition, our results showed significantly altered betweenness centrality located in right precuneus, calcarine, putamen, and left anterior cingulate in aMCI patients. Furthermore, association was found between network metrics and cognitive impairment. Our study suggests that the structural network properties might be preserved in SCD stage and disrupted in aMCI stage, which may provide novel insights into pathological mechanisms of AD.

As a non-contact optical experimental method, caustic method is commonly employed in measuring stress intensity factor at the crack tips of different materials. Caustics theory is commonly used for solving stress intensity factor at crack tips in homogeneous isotropic materials, but it lacks the required accuracy for solving stress intensity factor in interfacial cracks in dissimilar materials. In this paper, we have deduced the theoretical equation of stress intensity factor at interfacial crack tips the orthotropic bi-materials and evaluated the effects of different crack propagation speeds, orthotropic bi-materials and other parameters on the initial curves of focal line and the shape of caustics. In addition, dynamic caustic experiments on composite/epoxy bi-materials under low velocity-impact loadings were performed and the evolution of dynamic interfacial cracks was captured by high-speed cameras which showed good agreements with theoretical results. Research results confirmed the usefulness of the application of caustic method in dissimilar isotropic and orthotropic materials, isotropic-orthotropic bi-materials and homogeneous isotropic and orthotropic materials under subsonic crack propagation velocities.

Alzheimer’s disease (AD) is considered as a continuously pathological continuum. The AD pathophysiological process begins decades before the emergence of clinical symptoms. Recently, due to the advanced neuroimaging techniques and biochemical tests, various biomarkers are gradually identified, providing the ability to detect the evidence of AD pathology in the preclinical stage and further intervene the process of disease. Multimodal magnetic resonance imaging (MRI), with relatively non-invasive and economic benefits, is of great values to promote the clinical application. Therefore, researches involving brain structural and functional alterations in preclinical AD are summarized in this review.

Pathophysiological changes of Alzheimer's Disease (AD) begin decades before clinical symptoms become apparent, providing an important window for early diagnosis and intervention. Prodromal stage of AD, a great opportunity for effective treatment and postponing the disease onset, has drawn extensive attention. The application of different biomarkers including neuroimaging, biochemical substances and genes makes AD-related pathology detectable

The cell structures, locally micro-structures, combinations, electronic states as well as carrier transports induced by Oxygen vacancy for the CaMnO3 compound have been systematically investigated by pseudo-potential plane wave functions within the framework of density functional theory calculational method. The results reveal that the Oxygen vacant CaMnO2.75 has larger formation enthalpy than that of the intrinsic CaMnO3 and the Oxygen vacancy formation energy of CaMnO3 is as large as 7.10 eV. The Oxygen vacant CaMnO2.75 is harder to form than the intrinsic CaMnO3. The cubical orthorhombic structure tends to be rhombohedral. The lattice parameters a, b and c decrease simultaneously. The α and γ shrinks, the β increases. The lattice shrinkage induced by oxygen vacancy is anisotropic. The MnO6 octahedrons is twisted and it is shrinked along c and expanded along a. The bond strengths of Mn-O are all enhanced. There are six energy bands and the band gap is narrowed, the Fermi level is heightened and the electrons tend to occupy high energy bands. At the same time, the work function of electrons is lowered from 4.69872 eV to 4.00048 eV. The conductivity should be enhanced for Oxygen vacant CaMnO2.75, the O p and Mn d state electrons contribute most to the upper valance bands as well as the lower conduction bands, they jointly realize the conduction process. Keywords: CaMnO3, Oxygen vacancy, Formation, Electronic states

The e4 allele of the Apolipoprotein E gene (APOE-e4) is a potent genetic risk factor for sporadic Alzheimer’s disease (AD). Amnestic mild cognitive impairment (aMCI) is an intermediate state between normal cognitive aging and dementia, which is easy to convert to AD dementia. It is an urgent problem in the field of cognitive neuroscience to reveal the conversion of aMCI-e4 to AD. Based on our preliminary work, we will study the neuroimaging features in the special group of aMCI-e4 with multi-modality magnetic resonance imaging (structural MRI, resting state-fMRI and diffusion tensor imaging) longitudinally. In this study, 200 right-handed subjects who are diagnosed as aMCI with APOE-e4 will be recruited at the memory clinic of the Neurology Department, XuanWu Hospital, Capital Medical University, Beijing, China. All subjects will undergo the neuroimaging and neuropsychological evaluation at a 1 year-interval for 3 years. The primary outcome measures are 1) Microstructural alterations revealed with multimodal MRI scans including structure MRI (sMRI), resting state functional MRI (rs-fMRI), diffusion tensor imaging (DTI); 2) neuropsychological evaluation, including the World Health Organization-University of California-LosAngeles Auditory Verbal Learning Test (WHO-UCLA AVLT), Addenbrook’s cognitive examination-revised (ACE-R), mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating scale (CDR). This study is to find out the neuroimaging biomarker and the changing laws of the marker during the progress of aMCI-e4 to AD, and the final purpose is to provide scientific evidence for new prevention, diagnosis and treatment of AD. This study has been registered to ClinicalTrials.gov (NCT02225964, https://www.clinicaltrials.gov/ ) in August 24, 2014.

Individuals diagnosed with mild cognitive impairment (MCI) are at high risk of transition to Alzheimer’s disease (AD). However, little is known about functional characteristics of the conversion from MCI to AD. Resting-state functional magnetic resonance imaging was performed in 25 AD patients, 31 MCI patients, and 42 well-matched normal controls at baseline. Twenty-one of the 31 MCI patients converted to AD at approximately 24 months of follow-up. Functional connectivity strength (FCS) and seed-based functional connectivity analyses were used to assess the functional differences among the groups. Compared to controls, subjects with MCI and AD showed decreased FCS in the default-mode network and the occipital cortex. Importantly, the FCS of the left angular gyrus and middle occipital gyrus was significantly lower in MCI-converters as compared with MCI-nonconverters. Significantly decreased functional connectivity was found in MCI-converters compared to nonconverters between the left angular gyrus and bilateral inferior parietal lobules, dorsolateral prefrontal and lateral temporal cortices, and the left middle occipital gyrus and right middle occipital gyri. We demonstrated gradual but progressive functional changes during a median 2-year interval in patients converting from MCI to AD, which might serve as early indicators for the dysfunction and progression in the early stage of AD.

SummaryCD96, previously named T cell activation increased late expression (Tactile), is a transmembrane molecule that functions as an activated receptor on natural killer cells. It is well known that many transmembrane molecules have soluble forms, which were either shed from the cell surface or spliced at mRNA level. In many cases, the levels of soluble forms in the circulation could be used as biomarkers of lymphocyte activation in bacterial or virus infection, tumour, transplantation and autoimmue disease. To investigate whether CD96 could be released into the sera and the possible biological fuction of soluble hCD96 (sCD96), we generated and characterized five clones of anti-hCD96 mouse monoclonal antibodies (mAb) and developed a sandwich enzyme-linked immunosorbent assay (ELISA) system based on two anti-hCD96 mAbs with different epitope specificities. Using this ELISA system, sCD96 in serum samples from 99 healthy individuals could be detected. Furthermore, we found that the level of sCD96 in serum samples from patients with chronic viral hepatitis B or classes B and C of hepatic cirrhosis classified using the Child–Pugh score was much higher (P

Background Amnestic mild cognitive impairment (aMCI), which is recently considered as a high risk status for developing Alzheimer’s disease (AD), manifests with gray matter atrophy and increased focal functional activity in the medial temporal lobe (MTL). However, the abnormalities of whole-brain functional network connectivity in aMCI and its relationship to medial temporal atrophy (MTA) remain unknown. Methods In this study, thirty-six aMCI patients and thirty-five healthy controls (HCs) were recruited. Neuropsychological assessments and MTA visual rating scaling were carried out on all participants. Furthermore, whole brain functional network was constructed at voxel level, and functional connectivity strength (FCS) was computed as the sum of the connections for each node to capture its global integrity. General linear model was used to analyze the FCS values differences between aMCI and HCs. Then, the regions showing significant FCS differences were adopted as the imaging markers for discriminative analysis. Finally, the relationship between FCS values and clinical cognitive scores was correlated in patients with aMCI. Results Comparing to HCs, aMCI exhibited significant atrophy in the MTL, while higher FCS values within the bilateral MTL regions and orbitofrontal cortices. Notably, the right hippocampus had the highest classification power, with the area under receiver operating characteristics (ROC) curve (AUC) of 0.790 (confidence interval: 0.678, 0.901). Moreover, FCS values of the right hippocampus and the left temporal pole were positively correlated with the cognitive performance in aMCI. Conclusion This study demonstrated significantly structural atrophy and raised global functional integrity in the MTL, suggesting simultaneous disruption and compensation in prodromal AD. Increased intrinsic functional connectivity in the MTL may have the potential to discriminate subjects with tendency to develop AD.

To investigate the anti-inflammatory effect of bone marrow stromal cells (MSCs) transfected with recombinant adenovirus-mediated ciliary neurotrophic factor (CNTF) gene in C57BL/6 mice with experimental allergic encephalomyelitis (EAE).An adenovirus vector containing CNTF gene Ad-CNTF-IRES-GFP was constructed and transfected in the MSCs (MSC-CNTF). After examination of CNTF expression, the transfected cells were transplanted in C57BL/6 mice with MOG 35-55-induced EAE, which were monitored for the changes in the symptoms scores. The levels of tumor necrosis factor-alpha (TNF-alpha), inteferon-gamma (IFN-gamma), interleukin-12P35 (IL-12P35), and IL-10 in the peripheral blood of the mice were detected, and the number of MSC-CNTF cells in the spleen and spinal cord was counted. CD3+ T cell infiltration and TNF-alpha and IFN-gamma expressions in the lesions were also observed after the cell transplantation.CNTF gene transfection resulted in significantly increased CNTF expression in the MSCs. The mice receiving MSC-CNTF transplantation exhibited significantly improved symptoms with shortened disease course and lessened disease severity. The cell transplantation also resulted in significantly decreased peripheral blood TNF-alpha levels, ameliorated CD3+T cell infiltrations and lowered TNF-alpha expression in the lesions, while the levels of IFN-gamma underwent no significant changes.Transplantation of CNTF gene-transfected MSCs results in decreased peripheral blood TNF-alpha and IFN-gamma levels and reduced inflammatory cells, CD3-positive cells and TNF-alpha expression in the lesion of EAE, therefore providing better effect than MSCs in relieving the symptoms of EAE in mice.

CD226 is one of the main activating receptors on natural killer cells, and it can induce cytotoxicity to target cells through interaction with its ligands CD155 or CD112. CD226 is also involved in T cell differentiation, activation, and cytotoxicity. The expression of CD226 on natural killer cells and T cells can be regulated by cytokines and chemical stimuli; however, the mechanism of the regulation of the CD226 gene is still unknown. In this study, we have identified two promoters in the human CD226 gene named P1 and P2, which are located at –810 to –287 bp and +33 to +213 bp, respectively, and a negative regulation element between P1 and P2. Both P1 and P2 can be regulated by phorbol ester (12-O-tetradecanoylphorbol-13-acetate) and calcium ionophore (A23187). Bioinformatics analysis shows that, within this CD226 gene region, there are putative binding sites for transcription factors AP-1, Sp1, PEA3, and Ets-1. We have found that transcription factor activating protein-1 (AP-1) can up-regulate CD226 promoters P1 and P2 in human hepatocarcinoma cells, a hepatocarcinoma cell line with low expression of endogenous AP-1 and Ets-1. Interestingly, the transcription factor Ets-1 promotes AP-1-induced P2 activity but inhibits AP-1-induced P1 activity for which a 10-bp AP-1/Ets-1 composite site (CCTTCCTTCC) in P1 may be responsible.