Comparative Study on Topological Properties of the Whole-Brain Functional Connectome in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson's Disease Without RBD.

Purpose: Idiopathic rapid eye movement Sleep Behavior Disorder (iRBD) is considered as a prodromal and most valuable warning symptom for Parkinson's disease (PD). Although iRBD and PD without RBD (nRBD-PD) are both α-synucleinopathies, whether they share the same neurodegeneration process is not clear enough. In this study, the pattern and extent of neurodegeneration were investigated and compared between early-stage nRBD-PD and iRBD from the perspective of whole-brain functional network changes. Methods: Twenty-one patients with iRBD, 23 patients with early-stage nRBD-PD, and 22 matched healthy controls (HCs) were enrolled. Functional networks were constructed using resting-state functional MRI (fMRI) data. Network topological properties were analyzed and compared among groups by graph theory approaches. Correlation analyses were performed between network topological properties and cognition in the iRBD and nRBD-PD groups. Results: Both patients with iRBD and patients with early-stage nRBD-PD had attention, executive function, and some memory deficits. On global topological organization, iRBD and nRBD-PD groups still presented small-worldness, but both groups exhibited decreased global/local efficiency and increased characteristic path length. On regional topological organization, compared with HC, nRBD-PD presented decreased nodal efficiency, decreased degree centrality, and increased nodal shortest path length, while iRBD presented decreased nodal efficiency and nodal shortest path. For iRBD, brain regions with decreased nodal efficiency were included in the corresponding regions of nRBD-PD. Nodal shortest path changes were significantly different in terms of brain regions and directions between nRBD-PD and iRBD. Attention deficits were correlated with local topological properties of the occipital lobe in both iRBD and nRBD-PD groups. Conclusion: Both global and local efficiency of functional networks declined in nRBD-PD and iRBD groups. The overlaps and differences in local topological properties between nRBD-PD and iRBD indicate that iRBD not only shares functional changes of PD but also presents distinct features.

Abnormal Striatal-Cortical Networks Contribute to the Attention/Executive Function Deficits in Idiopathic REM Sleep Behavior Disorder: A Resting State Functional MRI Study.

INTRODUCTION: The structural and functional damages of the striatum were evident in idiopathic REM sleep behavior disorder (iRBD). With the research on iRBD deepens, cognitive impairment in iRBD is getting increasing attention. However, the mechanism of cognitive impairment in iRBD was poorly understood. METHODS: Neuropsychological assessment was carried out in 21 polysomnographies (PSGs) confirmed iRBD patients and 22 normal controls. Both regional homogeneity (ReHo) and seed-based functional connectivity (FC) rs-fMRI analyses were applied to explore the FC abnormalities and its association with cognition in iRBD patients. Positive ReHo clusters were set as seeds for further FC analysis. RESULTS: Idiopathic REM sleep behavior disorder patients presented cognitive deficits in attention/working memory, executive function, immediate memory, and visuo-spatial ability. ReHo analysis revealed abnormal spontaneous brain activities in the striatum (right caudate, left pallidum and bilateral putamen) in iRBD. FC analysis showed decreased striatum-related FCs in the frontal, temporal, occipital lobes, thalamus, anterior cingulate gyrus, as well as decreased intrinsic FCs between bilateral putamen and between caudate and pallidum. Deficits in attention/working memory, executive function, and immediate memory were associated with abnormal striatal-cortical FCs including frontal, temporal, and anterior cingulate cortices. CONCLUSION: Functional changes of striatum and cognitive impairment in iRBD were reconfirmed in the present study. Abnormal striatal-cortical networks, especially the striatal-frontal network, contribute to the working memory/executive function deficits in iRBDs. These findings supported the role of striatum not only in motor but also in cognition impairment in iRBD.

Noninvasive Identification of Renal Hypoxia in Experimental Myocardial Infarctions of Different Sizes by Using BOLD MR Imaging in a Mouse Model.

Purpose To test the feasibility of using blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging to measure alterations in renal oxygenation in a mouse model with experimental myocardial infarctions (MIs) of different sizes. Materials and Methods The study was approved by the local animal ethics committee. One hundred eighty-nine male C57BL/6 J mice were randomly subjected to MI surgery (with different locations of left anterior descending coronary artery occlusion) or sham surgery, defined as the exposure of the heart but no ligation. Mice with MI underwent late gadolinium enhancement imaging 1 day after occlusion to confirm infarct size. Mice were sorted into three groups: those with large MI (n = 48), those with small MI (n = 48), and those with sham operation (n = 36). Renal BOLD MR imaging was performed before and 1, 7, 14, 28, and 60 days after MI, and histologic analysis of renal hypoxia-inducible factor-1α (HIF-1α) and kidney injury molecule-1 (KIM-1) was performed to evaluate tissue hypoxia and kidney injury in subgroups imaged at each time point. The relationships between the BOLD R2* and HIF-1α expression and between HIF-1α and KIM-1 expression were assessed. Statistical analyses were performed with one-way analysis of variance or the Kruskal-Wallis test and Spearman correlation test. Results A significant elevation in R2* was detected in the MI groups compared with the sham group in the cortex (P < .001 for large MI vs sham group; P = .007 for small MI vs sham group) and medulla (P < .001 for large MI vs sham group; P = .003 for small MI vs sham group) on day 60, and R2* was higher in the large MI group than in the small MI group (P < .001). Renal HIF-1α expression was increased after MI and showed linear correlation with R2* in the cortex (R2 = 0.56) and medulla (R2 = 0.63). In addition, an increase in renal KIM-1 was observed in the MI groups compared with the sham group on day 60 (sham group, 53.9 × 103 arbitrary units [au] ± 35.2; large MI group, 389.3 × 103 au ± 99.8; and small MI group, 185.8 × 103 au ± 91.9; P < .001 for large MI group vs sham group; P = .037 for small MI group vs sham group), and renal KIM-1 showed a positive correlation with HIF-1α (R2 = 0.68). Conclusion The magnitude of renal hypoxia with MIs of different sizes can be noninvasively measured with BOLD MR imaging, and increased renal hypoxia is a potential risk factor for progressive tubulointerstitial injury in mouse kidneys. © RSNA, 2017 Online supplemental material is available for this article.

Diabetes mellitus stimulates pancreatic cancer growth and epithelial-mesenchymal transition-mediated metastasis via a p38 MAPK pathway.

Diabetes mellitus (DM) and its accompanying chronic inflammation promote tumor progression. p38 mitogen-activated protein kinase (MAPK) is an essential kinase for inflammation. The effects of p38 MAPK on epithelial-mesenchymal transition (EMT)-mediated diabetic pancreatic cancer metastasis remain unclear. Here, we demonstrate that p38 MAPK phosphorylation was significantly increased in pancreatic cancer cells treated with high glucose and in pancreatic tumors from diabetic animals. A p38 MAPK inhibitor significantly suppressed the proliferation and invasion of pancreatic cancer cells under high-glucose conditions. Moreover, p38 MAPK inhibition not only significantly decreased both the tumor volume monitored by magnetic resonance imaging and EMT-related metastasis but also increased the survival of diabetic mice bearing pancreatic tumors. Furthermore, the inflammation in diabetic animals bearing pancreatic tumors was also significantly lower after therapy. Collectively, our findings reveal that p38 MAPK inhibitors may provide a novel intervention strategy for diabetic pancreatic cancer treatment.

Role of P38 MAPK on MMP Activity in Photothrombotic Stroke Mice as Measured using an Ultrafast MMP Activatable Probe.

Matrix metalloproteinases (MMPs) exert a dual effect in ischemic stroke and thus represent an ideal target for detection and therapy. However, to date, all clinical trials of MMP inhibitors have failed, and alternative drug candidates and therapeutic targets are urgently required. Nonetheless, further investigations are limited by the lack of non-invasive imaging techniques. Here, we report a novel, fast and ultrasensitive MMP activatable optical imaging probe for the dynamic visualization of MMP activity in photothrombotic stroke mice. This probe provides a significant signal enhancement in as little as 15 min, with the highest signal intensity occurring at 1 h post-injection, and shows high sensitivity in measuring MMP activity alterations, which makes it specifically suitable for the real-time visualization of MMP activity and drug discovery in preclinical research. Moreover, using this probe, we successfully demonstrate that the regulation of the p38 mitogen-activated protein kinase (MAPK) signal pathway is capable of modulating MMP activity after stroke, revealing a novel regulatory mechanism of postischemic brain damage and overcoming the limitations of traditional therapeutic strategies associated with MMP inhibitors by using a non-invasive molecular imaging method.

Bone Marrow Endothelial Progenitor Cell Transplantation After Ischemic Stroke: An Investigation Into Its Possible Mechanism.

AIMS: We tested the hypothesis that endothelial progenitor cell (EPC)-mediated functional recovery after stroke may be associated with the endothelial nitric oxide synthase (eNOS)/brain-derived neurotrophic factor (BDNF) signaling pathway. METHODS: Mice were infused with either EPCs or saline after being subjected to middle cerebral artery occlusion. The EPC-treated mice also received intravenous injections of either Nω-nitro-l-arginine methyl ester (L-NAME, the NOS inhibitor) or saline. RESULTS: The activation of eNOS and the expression of BDNF were significantly increased in ischemic brain of the EPC-treated mice, along with increased angiogenesis and neurogenesis. On diffusion tensor imaging (DTI), significant increases in fractional anisotropy and fiber count were observed in white matter, indicating axonal growth stimulated by EPCs. However, the EPC-treated mice that were received an L-NAME injection failed to exhibit the observed increases in angiogenesis, neurogenesis, and axonal growth. In addition, the neurons cocultured with EPCs in vitro exhibited the increased expression of BDNF and decreased apoptosis after oxygen-glucose deprivation compared with the control group. This EPC-induced protective effect was virtually absent in the L-NAME treatment group. CONCLUSION: The eNOS/BDNF pathway may be involved in the EPC-mediated functional recovery of stroke mice. DTI is feasible for dynamically tracking the orientation of axonal projections after EPC treatment.

Visualizing myocardial inflammation in a rat model of type 4 cardiorenal syndrome by dual-modality molecular imaging.

Type 4 cardiorenal syndrome (CRS) is a life-threatening world health problem in which chronic kidney disease leads to progressive cardiovascular disease. In type 4 CRS, cardiac inflammation is an excellent target for both detection and therapy; however, this progression was underestimated by previous studies due to the lack of effective detection methods. To noninvasively visualize cardiac inflammation and monitor therapeutic efficacy of anti-inflammatory treatment in type 4 CRS, we here synthesized a dual-modality magneto-fluorescent nanoparticle (MNP) by combining ultrasmall superparamagnetic iron oxide nanoparticle and Rhodamine B for both magnetic resonance imaging (MRI) and optical imaging. This dual-functional MNP exhibited excellent performance such as high r2 relaxivity coefficient (283.4 mM(-1) s(-1)), high magnetism (96.7 emu/g iron) and a near neutral surface charge to minimize the reticuloendothelial system uptake. In vivo cardiac MRI showed significant negative contrast in the type 4 CRS rats, and the signal intensity on optical imaging was significantly higher in the type 4 CRS group compared with sham-operated and drug-treated groups. The specific targeting profile of MNPs to monocyte-macrophages was proven by histopathological analysis. Taken together, we demonstrate that this dual-modality strategy is feasible for noninvasively assessing myocardial inflammation and monitoring therapeutic efficacy in type 4 CRS.

Salvaging brain ischemia by increasing neuroprotectant uptake via nanoagonist mediated blood brain barrier permeability enhancement.

Ischemic stroke is a leading cause of adult disability and cognitive impairment worldwide. Neuroprotective therapy aims to save neurons by impeding the deleterious ischemic insults. However, the low efficiency of the neuroprotectants crossing blood brain barrier (BBB) prevents their clinical translation. In this work, a nanoagonist (NA) was developed to enhance neuroprotectant uptake by specifically increasing BBB permeability in brain ischemia. This NA first targeted ischemic brain vasculatures, temporarily opened local BBB by activating adenosine 2A receptors, and up-regulated the neuroprotectant uptake in brain ischemia. This NA significantly increased the delivery of superoxide dismutase (SOD), a free radical scavenger, into mouse brain ischemia. The combined treatment of NA/SOD achieved a five-fold ischemic volume reduction rate compared to the animal models treated with SOD alone. Non-invasive magnetic resonance imaging (MRI) confirmed the ischemia targeted BBB opening, increased brain drug delivery efficiency and up-regulated therapeutic response during the combined NA/SOD treatment. Since the inefficient brain drug delivery is a general problem for the treatment of central nervous system (CNS) diseases, this work provides a novel strategy to deliver therapeutics by crossing BBB with high efficiency and targeting specificity.

Synergistic Effects of Transplanted Endothelial Progenitor Cells and RWJ 67657 in Diabetic Ischemic Stroke Models.

BACKGROUND AND PURPOSE: An immature vascular phenotype in diabetes mellitus may cause more severe vascular damage and poorer functional outcomes after stroke, and it would be feasible to repair damaged functional vessels using endothelial progenitor cell (EPC) transplantation. However, high glucose induces p38 mitogen-activated protein kinase activation, which can accelerate the senescence and apoptosis of EPCs. The aim of this study was to investigate the combined effects of EPC transplantation and p38 mitogen-activated protein kinase inhibitor administration on diabetic stroke outcomes. METHODS: Bone marrow-derived EPCs were injected intra-arterially into db/db mice after ischemic stroke induction. RWJ 67657 (RWJ), a p38 mitogen-activated protein kinase inhibitor, was administered orally for 7 consecutive days, with the first dose given 30 minutes before stroke induction. Functional outcome was determined at days 0, 1, 7, 14, and 21. Angiogenesis, neurogenesis, infarct volume, and Western blotting assays were performed on day 7, and white matter remodeling was determined on day 14. RESULTS: Neither EPC transplantation nor RWJ administration alone significantly improved diabetic stroke outcome although RWJ displayed a potent anti-inflammatory effect. By both improving the functioning of EPCs and reducing inflammation, EPC transplantation plus RWJ administration in vivo synergistically promoted angiogenesis and neurogenesis after diabetic stroke. In addition, the white matter remodeling, behavioral scores, and expressions of vascular endothelial growth factor and brain-derived neurotrophic factor were significantly increased in diabetic mice treated with both EPCs and RWJ. CONCLUSIONS: The combination of EPC transplantation and RWJ administration accelerated recovery from diabetic stroke, which might have been caused by increased levels of proangiogenic and neurotrophic factors.

Non-invasive monitoring of transplanted endothelial progenitor cells in diabetic ischemic stroke models.

Endogenous endothelial progenitor cells (EPCs) are functionally impaired in hyperglycemia through the p38 MAPK signaling pathway. However, the number and function of transplanted exogenous EPCs in diabetic animals remains unclear. The objectives of this study were to establish a non-invasive imaging strategy to monitor the homing of transplanted EPCs in diabetic stroke mice and to assess the effect of RWJ 67657, an inhibitor of p38 MAPK, on the homing ability of exogenous EPCs. Bone marrow-derived EPCs were labeled in vitro with a multi-functional nanoprobe modified with paramagnetic chelators and fluorophores before being infused into stroke mice. The signal of the nanoprobe reached its peak on day 5 in both magnetic resonance imaging and near-infrared fluorescence imaging after EPC transplantation in wild-type stroke models. The signal enhancement of diabetic stroke models was significantly lower than that of wild-type controls. However, the signal intensity of diabetic stroke models significantly increased after oral administration of RWJ 67657, indicating that more transplanted EPCs migrated to the ischemic brain. Furthermore, the increased exogenous EPCs induced remarkably greater angiogenesis after stroke. These results suggest that this dual-modal imaging strategy is feasible for non-invasively monitoring transplanted cells in vivo.

Synthesis of gold nanorods and their functionalization with bovine serum albumin for optical hyperthermia.

Although gold nanorods (GNRs) have been investigated extensively for optical hyperthermia therapies, the synthesis of rods is far from ideal. In this report, we optimized the synthesis of gold nanorods using hydroquinone as a reducing agent. Compared with the GNRs prepared by traditional ways, the as-synthesized rods have a flexibly tunable size and wider range of longitudinal surface plasmon resonance (LSPR). Furthermore, a series of small-length gold nanorods with length ranging from 30 to 90 nm were synthesized and they are more suitable for in vivo biomedical applications. Finally, we exploited a convenient approach for preparing water-soluble GNRs with less toxicity, better dispersion and flexible functionalization by exchanging hexadecyltrimethylammonium bromide (CTAB) on the surface of the rods with carboxylated bovine serum albumin (BSA) derivative, the BSA modified GNRs showed significant anticancer efficacy through near infrared (NIR) hyperthermia. We believe that the as-prepared gold nanorods will find promising applications in biomedical fields, especially in cancer therapy.

Multimodal nanoprobes evaluating physiological pore size of brain vasculatures in ischemic stroke models.

Ischemic stroke accounts for 80% strokes and originates from a reduction of cerebral blood flow (CBF) after vascular occlusion. For treatment, the first action is to restore CBF by thrombolytic agent recombinant tissue-type plasminogen activator (rt-PA). Although rt-PA benefits clinical outcome, its application is limited by short therapeutic time window and risk of brain hemorrhage. Different to thrombolytic agents, neuroprotectants reduce neurological injuries by blocking ischemic cascade events such as excitotoxicity and oxidative stress. Nano-neuroprotectants demonstrate higher therapeutic effect than small molecular analogues due to their prolonged circulation lifetime and disrupted blood-brain barrier (BBB) in ischemic region. Even enhanced BBB permeability in ischemic territories is verified, the pore size of ischemic vasculatures determining how large and how efficient the therapeutics can pass is barely studied. In this work, nanoprobes (NPs) with different diameters are developed. In vivo multimodal imaging indicates that NP uptakes in ischemic region depended on their diameters and the pore size upper limit of ischemic vasculatures is determined as 10-11 nm. Additionally, penumbra defined as salvageable ischemic tissues performed a higher BBB permeability than infarct core. This work provides a guideline for developing nano-neuroprotectants by taking advantage of the locally enhanced BBB permeability in ischemic brain tissues.

Image-guided pro-angiogenic therapy in diabetic stroke mouse models using a multi-modal nanoprobe.

PURPOSE: The efficacy of pro-angiogenic therapy is difficult to evaluate with current diagnostic modalities. The objectives were to develop a non-invasive imaging strategy to define the temporal characteristics of angiogenesis and to evaluate the response to pro-angiogenic therapy in diabetic stroke mouse models. METHODS: A home-made ανß3 integrin-targeted multi-modal nanoprobe was intravenously injected into mouse models at set time points after photothrombotic stroke. Magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging were carried out at 24 h post-injection. Bone marrow-derived endothelial progenitor cells (EPCs) were infused into the mouse models of ischemic stroke to stimulate angiogenesis. RESULTS: The peak signal intensity in the ischemic-angiogenic area of diabetic and wild-type mouse models was achieved on day 10, with significantly lower signal enhancement observed in the diabetic models. Although the signal intensity was significantly higher after EPC treatment in both models, the enhancement was less pronounced in the diabetic animals compared with the wild-type controls. Histological analysis revealed that the microvessel density and expression of ß3 integrin were correlated with the signal intensity assessed with MRI and NIRF imaging. CONCLUSIONS: The non-invasive imaging method could be used for early and accurate evaluation of the response to pro-angiogenic therapy in diabetic stroke models.

Non-invasively evaluating therapeutic response of nanorod-mediated photothermal therapy on tumor angiogenesis.

Gold nanorod-mediated photothermal therapy has been widely explored for cancer treatment. However, timely evaluation of the therapeutic response is difficult as current diagnostic approaches are largely based on measurements of tumor volume. The present study developed a non-invasive imaging strategy to rapidly assess the efficacy of photothermal therapy in mice bearing human tumor xenografts. In this study, gold nanorods modified with carboxylated bovine serum albumin showed both anti-tumor and anti-angiogenesis effects under near-infrared laser irradiation. An α(v)ß3 integrin-targeted multi-modal nanoprobe, Dendrimer-arginine-glycine-aspartic acid (Den-RGD), was designed and intravenously injected into mice bearing tumor xenografts at 24 h after photothermal therapy. Magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging demonstrated that the Den-RGD not only visualized the tumors with high target-to-background ratio, but also showed the ability to evaluate the therapeutic response by monitoring the tumor neovasculature. Additionally, the target-to-background ratio on MRI and NIRF imaging correlated with the microvessel density in the Den-RGD groups. Immunofluorescence staining confirmed the targeting specificity of Den-RGD to the neovasculature at the tumor periphery. This dual-modal imaging method holds the promise of evaluating therapeutic efficacy in vivo. Nanomedicine provides a multi-functional platform for treatment of cancer and image-guided assessment of anti-cancer therapy.

Renal lipids and oxygenation in diabetic mice: noninvasive quantification with MR imaging.

PURPOSE: To determine the relationship between renal lipid content and intrarenal oxygenation in diabetic nephropathy by using noninvasive chemical shift-selective (CSS) imaging and blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging. MATERIALS AND METHODS: The study was approved by the institutional Committee on Animal Research. Lipid and water phantoms for CSS imaging were made, and BOLD MR imaging phantoms from arterial and venous blood samples were collected from rats. CSS imaging and BOLD imaging were performed to measure lipid contents and T2* in phantoms and kidneys of diabetic gene (db) db/db mice and wild-type mice after exposure to nitrogen (four per group) and injection of furosemide (four per group). Results of MR imaging-measured lipid contents and oxygen tension were compared with known values in phantoms and reference standard from mice with histologic data. Statistical analysis was performed with independent sample and paired sample t tests and Pearson correlation test. RESULTS: Renal lipid content in db/db mice was significantly higher compared with that in control mice (9.40% ± 1.89 and 3.11% ± 0.57, respectively; P < .001). In addition, the lipid content in the cortex of db/db mice was significantly higher than that in medulla (12.73% ± 0.94 and 3.16% ± 0.50, respectively; P < .001). Correlation was significant between T2* measured with BOLD and oxygen tension in blood phantoms (r = 0.958; P < .001). Lower baseline T2* in diabetic kidney suggested lower oxygenation that reserved excess oxygen supply. Lower oxygenation in diabetic kidney cortex was observed after nitrogen exposure and furosemide injection. CONCLUSION: Noninvasive CSS imaging and MR imaging of db/db diabetic mice revealed the relationship between the renal lipid content and intrarenal oxygenation in diabetic kidney. Lipid accumulation in diabetic kidney compromises the oxygenation of the renal tissue and made it more susceptible to renal hypoxia. Online supplemental material is available for this article.

[Effects of telmisartan on the level of Aß1-42, interleukin-1ß, tumor necrosis factor α and cognition in hypertensive patients with Alzheimer's disease].

OBJECTIVE: To explore the effects of telmisartan, an angiotensin II type 1 receptor blocker with peroxisome proliferator-activated receptor γ-stimulating activity, on the levels of Aß1-42, interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α) and cognition in elderly hypertensive patients with Alzheimer's disease (AD). METHODS: A total of 48 patients with probable AD and essential hypertension were randomly assigned into telmisartan group (n = 24, 40 - 80 mg qd) or amlodipine group (n = 24, 5 - 10 mg qd) for 6 months at Henan Provincial People's Hospital during 2008 - 2011. Cognitive evaluations were assessed at pre-treatment and 24 weeks post-treatment by clinical assessment, rating scales and neuropsychological tests while the cerebrospinal fluid (CSF) levels of Aß1-42, IL-1ß and TNF-α by enzyme-linked immunosorbent assay (ELISA). RESULTS: After 6 months, mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) significantly decreased compared with baseline values to a similar extent in both groups. No significant differences existed between two groups in SBP or DBP. The patients displayed significantly higher Aß1-42 and greatly lower levels of IL-1ß and TNF-α in the telmisartan group versus the amlodipine group (P < 0.05). At 24 weeks, the patients in the telmisartan group had better mini-mental state examination (MMSE) (22.0 ± 3.4) and Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) (15 ± 5) scales scores than those taking amlodipine (MMSE (19.5 ± 2.8) and ADAS-cog (18 ± 5). Patients treated with telmisartan had better improvement on the MMSE (P < 0.05) and ADAS-cog (P < 0.05) scales compared with the amlodipine group by the end of study week 24. CONCLUSION: Telmisartan may delay the decreased level of Aß1-42 and reduce the levels IL-1ß and TNF-α in CSF so as to improve the cognitive function of elderly hypertensive patients with AD. With additional benefits in comparison with common antihypertensive drugs, it may offer a novel therapeutic strategy of AD.

Photophysics of the lanthanide complexes with conjugated carboxylic acids by low temperature fluorescent spectroscopy.

In the context, some lanthanide (Eu(3+), Tb(3+) and Sm(3+)) complexes with conjugated carboxylic acids (pyridine-carboxylic acids derivatives) have been synthesized and characterized. The low temperature fluorescent spectra for these complexes have been measured at nitrogen atmosphere (77 K), indicating that the central Ln(3+) ions locate in an equivalent coordination environment with low symmetry for most of these lanthanide complexes belonging to dimeric or polymeric structure. Therefore, the electronic dipole transition (supersensitive transition) ((5)D(0) --> (7)F(2) for Eu(3+), (5)D(4) --> (7)F(6) for Tb(3+), (4)G(5/2) --> (6)H(9/2) for Sm(3+)) and magnetic dipole transition ((5)D(0) --> (7)F(1) for Eu(3+), (5)D(4) --> (7)F(5) for Tb(3+), (4)G(5/2) --> (6)H(5/2) for Sm(3+)) show the regular change in the corresponding split number of fluorescent spectra, which can be realized to predict the fine structure of lanthanide complexes.