Reservoir of human immunodeficiency virus in the brain:New insights into the role of T cells

Human immunodeficiency virus(HIV)infection of the central nervous system(CNS)has attracted significant attention because it contributes to severe complications of acquired immunodeficiency syndrome(AIDS)and seriously impairs the life quality of infected patients.In this review,we briefly describe the latent infection of HIV in CNS and focus on the role of the important immune cells,such as T cells,in the formation and maintenance of the HIV reservoir in CNS.This review explores the mechanisms by which T cells enter CNS and establish latent infection of HIV in the CNS.In conclusion,we summarize the role of these cells in the interaction between HIV and CNS.With our better understanding of the underlying mechanisms,we propose future directions for the development of novel strategies to eliminate HIV reservoirs in the CNS based on cellular components.

Caspase-1 inhibition attenuates activation of BV2 microglia induced by LPS-treated RAW264.7 macrophages

Neuroinflammation has been recognized as a factor in the pathogenesis of neurodegenerative diseases.Emerging evidence suggests that peripheral inflammation,besides neuroinflammation,functions as a modulator of disease progression and neuropathology in several neurodegenerative diseases.However,detailed correlations among peripheral inflammation,neuroinflammation and neurodegeneration remain unknown.In the present study,we prepared a peripheral inflammation model with lipopolysaccharides(LPS)-stimulated RAW264.7 macrophages to explore its activation on BV2 microglia.We found that LPS induced the production of IL-1 β,IL-6 and TNF-α in the culture medium of RAW264.7 macrophages.We further showed that LPS plus ATP activated inflammasome,evidenced by the upregulation of caspase-1 and IL-1β,which was suppressed by ZYVAD,a caspase-1 inhibitor.Furthermore,the conditioned medium obtained from LPS-treated RAW264.7 macrophages activated BV2 microglia,stimulating the release of IL-1β,IL-6 and TNF-a from BV2 cells.ZYVAD pretreatment markedly suppressed BV2 microglia activation induced by RAW264.7 cells conditioned medium.Taken together,our study indicates that macrophage-mediated peripheral inflammation subsequently evokes neuroinflammation and may aggravate neural damage.Inflammasome and caspase-1 may be potential targets for modulating systemic inflammatory responses in neurodegenerative diseases.

Subjective poor sleep quality in Chinese patients with Parkinson's disease without dementia

Parkinson's disease (PD) is a common progressive neurological disorder and is composed of motor and nonmotor symptoms. Sleep disturbances are frequent problems for patients with PD. The relationship between sleep disturbances with Hoehn and Yahr (H&Y) staging have been demonstrated. However, the relationship between sleep disorders and H&Y is still unclear in patients with PD without dementia in Chinese PD patients. In this study, we interviewed 487 non-demented PD patients of Chinese Han descents by H&Y classification. We found that night sleep quality was significantly associated with the severity of PD (P=0.008). Panic disorder severity scale (PDSS) total scores were correlated with PD non-motor symptoms scale (PDNMS) scores (r=-0.528, P<0.001), the Hamilton depression scale (HAMD) scores (r=-0.545, P<0.001) and the Hamilton anxiety scale (HAMA) scores (r=-0.498, P<0.001). Our results indicated that sleep quality deteriorated with the advancing of PD in Chinese non-demented patients with PD. Depression and anxiety may partly explain sleep disturbances in nondemented patients with PD.

Pretreatment with simvastatin upregulates expression of BK-2R and CD11b in the ischemic penumbra of rats

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductases, collectively known as statins, have been shown to minimize cerebral ischemic events in patients. We assessed the mechanisms of simvastatin pretreatment in preventing cerebral ischemia/reperfusion injury in rats using a model of middle cerebral artery occlusion(MCAO).Rats were pretreated with simvastatin 14 days prior to MCAO induction. At 3, 24, and 48 hours after reperfusion,bradykinin levels in the ischemic penumbra were assayed by ELISA, mRNA levels of bradykinin B2 receptors(BK-2Rs) and CD11b were measured by fluorescent quantitative real-time PCR(RT-PCR), and co-expression of microglia and BK-2Rs was determined by immunofluorescence. Simvastatin had no effect on bradykinin expression in the ischemic penumbra at any time point. However, the levels of BK-2R and CD11b mRNA in the ischemic penumbra,which were significantly decreased 3 hours after ischemia-reperfusion, were increased in simvastatin-pretreated rats.Moreover, the co-expression of BK-2Rs and microglia was confirmed by immunofluorescence analysis. These results suggest that the beneficial effects of simvastatin pretreatment before cerebral ischemia/reperfusion injury in rats may be partially due to increased expression of BK-2R and CD11b in the ischemic penumbra.

Granulocyte-macrophage colony-stimulating factor-transfected bone marrow stromal cells for the treatment of ischemic stroke

Adult,male,Sprague-Dawley rats were injected with granulocyte-macrophage colony-stimulating factor-transfected bone marrow stromal cells(GM-CSF-BMSCs) into the ischemic boundary zone at 24 hours after onset of middle cerebral artery occlusion.Results showed reduced infarct volume,decreased number of apoptotic cells,improved neurological functions,increased angiogenic factor expression,and increased vascular density in the ischemic boundary zone in rats that underwent GM-CSF-BMSCs transplantation compared with the BMSCs group.Experimental findings suggested that GM-CSF-BMSCs could serve as a potential therapeutic strategy for ischemic stroke and are superior to BMSCs alone.

Atomic scale investigation of FCC→HCP reverse phase transformation in face-centered cubic zirconium

Mechanism of FCC→HCP reverse phase transformation in face-centered cubic zirconium(FCC-Zr)along with a concomitant 70.5°rotation ofα-Zr matrix were investigated in zircaloy-4(Zr-4)cladding tube by using transmission electron microscopy(TEM).Results showed that the interaction among a secondary phase particle(SPP)and three FCC-Zr grains resulted in the formation of cross stacking faults in SPP and exerted a drag force on minor axis of the adjacent FCC-Zr phase.Moreover,when the shear stress along[112]_(FCC-Zr)direction was large enough to initiate the emission of 1/6[112]Shockley partial dislocation on every other(111)_(FCC-Zr)close-packed plane,the stacking sequence would change from ABC ABCA to AB ABABA viz.(0001)planes of the daughter HCP phase.Thus,FCC→HCP reverse phase transformation in FCC-Zr was presented.

TC11钛合金中α″相和α′相的组织演变和显微硬度

研究了TC11钛合金中α"相和α'相的显微组织转变和显微硬度。金相显微组织观察和X射线衍射分析的结果表明:随着固溶温度的提高α"相逐渐向α'相的晶体结构转变,α相、α"相和α'相的显微组织演变规律为:α+α",α+α"+α',α+α',α'。显微硬度测试的结果表明:在935~995℃固溶后显微硬度随着温度的提高先增大后减少,在985℃固溶后显微硬度达到峰值。综合分析显微组织影响合金显微硬度的机理:在935~985℃固溶后α'片层的厚度和间距变化的幅度小,β转变组织长大缓慢,在β转变组织中先后析出α"和α'相,随着固溶温度的提高α'片层的含量随之提高产生了相变强度效果,使其显微硬度提高;在985~995℃固溶后α'片层的厚度和间距明显增大,β转变组织变粗大,α"相消失,α'相的含量降低,相变强化的效果减弱,使β转变组织的显微硬度降低。

The influence of microtexture on the formation mechanism of nodules in Zircaloy-4 alloy tube

Corrosion re sistance of Zircaloy-4 alloy tube in superheated steam at 673 K/10.3 MPa is anisotropic.A part of the surface undergoes uniform corrosion while the other suffers nodular corrosion.Narrow and wide nodules are observed after an exposure period of 3 and 30 days,respectively.A new matrix transformation method is established in order to study the formation mechanism of nodules in the cross-section(CS) of Zircaloy-4 alloy tube using the EBSD technique,while the CS perpendicular to axial direction(AD).The results reveal that the microtexture is a key factor behind the two types of corrosion.Furthermore,the oxide layers grow anisotropically over the corroded surface.A thick oxide layer forms over the nodular corrosion region on the grains with c-axis oriented in the range of 40° around tangential direction(TD),whereas a thin oxide layer over the uniform corrosion region is detected on the grains with c-axis oriented in the range of 68° around TD.In short,the anisotropic growth of oxide layer was caused by the change of microtexture of the Zr-4 alloy tube,and this anisotropic growth of oxide layer contributed to the nodules formation.

Deformation twinning in octahe dron-base d face-centere d cubic metallic structures:Localized shear-force dipoles drive atomic displacements

Twinning is found to impart favorable mechanical,physical and chemical properties to nanostructured materials.Deformation twinning prevails in face-centered cubic(FCC)nanocrystalline materials upon loading.In FCC structures,the<112>{111}deformation twinning is traditionally believed to nucleate and grow through layer-by-layer emission of 1/6<112>Shockley partial dislocations on consecutive{111}planes.We report that deformation twinning is able to occur in crystalline(Fe,Nb)_(23)Zr_(6)nanoparticles(NPs)that have a large Mn 23 Th 6-type FCC structure with a Zr-octahedron as a motif.Based on direct atomic-scale observations,we discover a new zero-net-strain path for the<112>{111}deformation twin-ning in FCC structures.To form a[¯1¯12]/(111)twin,for example,short(¯1¯11)planes within two adjacent(111)plane layers in the repeated three-layer sequence of(111)planes are shear deformed continuously by a shear-force dipole along the[11¯2]direction like a domino effect,whereas the other(111)plane in the repeated sequence remains intact.In addition,a loading criterion for deformation twinning of a FCC NP under uniaxial compression is proposed based on our observations.Our work here not only extends the fundamental understanding on deformation twinning in FCC structures,but also opens up studies of deformation behaviors in a class of Mn 23 Th 6-type FCC materials.

Intermediate state of hexagonal close-packed structure to face-centered cubic structure transformation: Direct evidence for basal-type face-centered cubic phase via partial dislocation in zirconium

1.Introduction Zirconium(Zr)and its alloys show great applications in nuclear and chemical industry thanks to their appropriate mechanical properties,low thermal neutron absorption cross-section and excellent corrosion resistance[1–3].Zr displays three different crystal structures on the temperature-pressure phase diagram:the hexagonal close-packed structure(HCP,α-Zr),the body centered cubic structure(BCC,β-Zr)and the simple hexagonal structure(ω-Zr).

A new type face-centered cubic zirconium phase in pure zirconium

So far,only two orientation relationships(OR)between hexagonal close-packed(HCP)(αphase)and facecentered cubic(FCC)structures in zirconium and titanium alloys have been reported.Here a new type FCC phase(named γ phase)with OR:<11■0>_(α)‖<100>_(γ) and{0001}_(α)‖{002}_(γ) was observed for the first time in annealed pure zirconium by means of transmission electron microscopy(TEM)technique.The α→γ phase transformation can be accomplished via expansion along[1■00]direction and slip of Shockley partial dislocation with 1/3[1■00]on(0001)basal planes.

Nano-refinement of the face-centered cubic Zr(Fe,Cr)_(2)secondary phase particles in Zircaloy-4 alloy via localized-shearing/bending-driven fracture under high-temperature compression

Nanoparticles are extensively introduced to improve the mechanical,physical,and chemical properties of alloys.In the present study,the underlying nano-refinement mechanisms of face-centered cubic Zr(Fe,Cr)_(2)secondary phase particles(SPPs)that precipitated in Zircaloy-4 alloy under high-temperature compression were investigated in detail by utilizing high-resolution transmission electron microscopy(HRTEM)and conventional TEM techniques.The frequently observed Zr(Fe,Cr)_(2)SPPs were incoherent with the matrix and exhibited brittle fracture behaviors without measurable plasticity.HRTEM observations revealed two mechanisms underlying the nano-refinement of incoherent micro-sized SPPs via localized shear fracture on{11¯2}SPP and nanoprecipitate-assisted bending fracture,respectively.The latter was,for the first time,found to occur when the movements of large SPPs were blocked by nanometer-sized SPP during alloy deformation.Accordingly,two force models were proposed to visualize their potential nano-refinement processes.The knowledge attained from this study sheds new light on the deformation behaviors of Zr(Fe,Cr)_(2)SPPs and their associated size refinement mechanisms under high-temperature compression,and is expected to greatly benefit the process optimization of zirconium alloys to achieve precipitate nano-refinement.