C-X-C chemokine receptor type 7 antibody enhances neural plasticity after ischemic stroke

Stromal cell-derived factor-1 and its receptor C-X-C chemokine receptor 4(CXCR4) have been shown to regulate neural regeneration after stroke.Howeve r,whether stromal cell-derived factor-1 receptor CXCR7,which is widely distributed in the develo ping and adult central nervous system,participates in neural regeneration remains poorly unde rstood.In this study,we established rat models of focal cerebral ischemia by injecting endothelin-1 into the cerebral co rtex and striatum.Starting on day 7 after injury,CXCR7-neutralizing antibody was injected into the lateral ventricle using a micro drug delivery system for 6 consecutive days.Our results showed that CXCR7-neutralizing antibody increased the total length and number of sprouting co rticospinal tra ct fibers in rats with cerebral ischemia,increased the expression of vesicular glutamate transporter 1 and growth-related protein 43,marke rs of the denervated spinal cord synapses,and promoted the differentiation and maturation of oligodendrocyte progenitor cells in the striatum.In addition,CXCR7 antibody increased the expression of CXCR4 in the striatum,increased the protein expression of RAS and ERK1/2 associated with the RAS/ERK signaling pathway,and im proved rat motor function.These findings suggest that CXCR7 improved neural functional recovery after ischemic stroke by promoting axonal regeneration,synaptogenesis,and myelin regeneration,which may be achieved by activation of CXCR4 and the RAS/ERK1/2 signaling pathway.

Effects of CXCR7-neutralizing antibody on neurogenesis in the hippocampal dentate gyrus and cognitive function in the chronic phase of cerebral ischemia

Stromal cell-derived factor-1 and its receptor CXCR4 are essential regulators of the neurogenesis that occurs in the adult hippocampal dentate gyrus.However,the effects of CXCR7,a new atypical receptor of stromal cell-derived factor-1,on hippocampal neurogenesis after a stroke remain largely unknown.Our study is the first to investigate the effect of a CXCR7-neutralizing antibody on neurogenesis in the dentate gyrus and the associated recovery of cognitive function of rats in the chronic stage of cerebral ischemia.The rats were randomly divided into sham,sham+anti-CXCR7,ischemia and ischemia+anti-CXCR7 groups.Endothelin-1 was injected in the ipsilateral motor cortex and striatum to induce focal cerebral ischemia.Sham group rats were injected with saline instead of endothelin-1 via intracranial injection.Both sham and ischemic rats were treated with intraventricular infusions of CXCR7-neutralizing antibodies for 6 days 1 week after surgery.Immunofluorescence staining with doublecortin,a marker for neuronal precursors,was performed to assess the neurogenesis in the dentate gyrus.We found that anti-CXCR7 antibody infusion enhanced the proliferation and dendritic development of doublecortin-labeled cells in the dentate gyrus in both ischemic and sham-operated rats.Spatial learning and memory functions were assessed by Morris water maze tests 30-32 days after ischemia.CXCR7-neutralizing antibody treatment significantly reduced the escape latency of the spatial navigation trial and increased the time spent in the target quadrant of spatial probe trial in animals that received ischemic insult,but not in sham operated rats.These results suggest that CXCR7-neutralizing antibody enhances the neurogenesis in the dentate gyrus and improves the cognitive function after cerebral ischemia in rats.All animal experimental protocols and procedures were approved by the Institutional Animal Care and Use Committee of China Medical University(CMU16089 R)on December 8,2016.

Parametrized post-Newtonian secular transit timing variations for exoplanets

Ground-based and space-borne observatories used for studying exoplanet transits now and in the future will considerably increase the number of exoplanets known from transit data and the precision of the measured times of transit minima.Variations in the transit times can not only be used to infer the presence of additional planets,but might also provide opportunities to test the general theory of relativity in these systems.To build a framework for these possible tests,we extend previous studies on the observability of the general relativistic precessions of periastron in transiting exoplanets to variations in secular transit timing under parametrized post-Newtonian formalism.We find that if one can measure the difference between observed and predicted variations of general relativistic secular transit timing to 1 s yr-1in a transiting exoplanet system with a Sun-like mass,a period of;day and a relatively small eccentricity of;.1,general relativity will be tested to the level of;%.

Theoretical characterization of hole mobility in BTBPD

（ E）-5,5＇-Bis（ 5-（ benzo[ b ]thiophen- 2-yl ）thiophen-2-yl ）-1,1＇-bis（ 2-ethylhexyl ）-[ 3,3＇-bipyrrolylidene ]- 2,2＇（1H, l＇H）-dione （BTBPD） has been reported by Zhang and co-workers. To further understand the charge-transporting nature of BTBPD, the density-functional theory （DFF） and the Marcus charge transfer theory were performed. The character of the frontier molecular orbitals, reorganization energies and transfer integrals in different directions were considered in details. The results revealed that the BTBPD has high hole transport efficiency （μ = 0.29 cm2 V-1 s-1 ）. The intermolecular π-π interaction and S...S interaction provide the holes transport channels.