Group 2 innate lymphoid cells suppress the pathology of neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is a severe central nervous system (CNS) autoimmune disease that primarily damages the optic nerves and spinal cord. Group 2 innate lymphoid cells (ILC2) are potent producers of type 2 cytokines that orchestrate immune and inflammatory responses. However, the role of ILC2 in CNS autoimmune diseases remains unknown. In patients with NMOSD, we identified a significant reduction of ILC2 in peripheral blood, which was correlated with disease severity. Using a mouse model of NMOSD induced by intracerebral injection of NMOSD-IgG with complement, we found CNS infiltration of ILC2 mainly expressing interleukin (IL)-5 and IL-13. The depletion of ILC2 led to increased CNS lesion volume, reduced CNS glucose metabolism, and augmented astrocyte injury and demyelination. The exacerbated NMOSD pathology was accompanied by increased accumulation of Iba1+ cells and complement activity in CNS lesions. In addition, the expansion of ILC2 using IL-33 attenuated NMO pathology. Collectively, these findings suggest a beneficial role of ILC2 in NMOSD, which deserves further investigation for future design of immune therapies to treat patients with NMOSD.

A translocator protein 18 kDa agonist protects against cerebral ischemia/reperfusion injury.

BACKGROUND: Cerebral ischemia is a leading cause of death and disability with limited treatment options. Although inflammatory and immune responses participate in ischemic brain injury, the molecular regulators of neuroinflammation after ischemia remain to be defined. Translocator protein 18 kDa (TSPO) mainly localized to the mitochondrial outer membrane is predominantly expressed in glia within the central nervous system during inflammatory conditions. This study investigated the effect of a TSPO agonist, etifoxine, on neuroinflammation and brain injury after ischemia/reperfusion. METHODS: We used a mouse model of middle cerebral artery occlusion (MCAO) to examine the therapeutic potential and mechanisms of neuroprotection by etifoxine. RESULTS: TSPO was upregulated in Iba1+ or CD11b+CD45int cells from mice subjected to MCAO and reperfusion. Etifoxine significantly attenuated neurodeficits and infarct volume after MCAO and reperfusion. The attenuation was pronounced in mice subjected to 30, 60, or 90 min MCAO. Etifoxine reduced production of pro-inflammatory factors in the ischemic brain. In addition, etifoxine treatment led to decreased expression of interleukin-1ß, interleukin-6, tumor necrosis factor-α, and inducible nitric oxide synthase by microglia. Notably, the benefit of etifoxine against brain infarction was ablated in mice depleted of microglia using a colony-stimulating factor 1 receptor inhibitor. CONCLUSIONS: These findings indicate that the TSPO agonist, etifoxine, reduces neuroinflammation and brain injury after ischemia/reperfusion. The therapeutic potential of targeting TSPO requires further investigations in ischemic stroke.

Crossover from 3D to 2D quantum transport in Bi2Se3/In2Se3 superlattices.

The topological insulator/normal insulator (TI/NI) superlattices (SLs) with multiple Dirac channels are predicted to offer great opportunity to design novel materials and investigate new quantum phenomena. Here, we report first transport studies on the SLs composed of TI Bi2Se3 layers sandwiched by NI In2Se3 layers artificially grown by molecular beam epitaxy (MBE). The transport properties of two kinds of SL samples show convincing evidence that the transport dimensionality changes from three-dimensional (3D) to two-dimensional (2D) when decreasing the thickness of building block Bi2Se3 layers, corresponding to the crossover from coherent TI transport to separated TI channels. Our findings provide the possibility to realizing "3D surface states" in TI/NI SLs.

Prediction of a new two-dimensional metallic carbon allotrope.

By means of the first-principles calculations, we predict a new metallic two-dimensional carbon allotrope named net W with Cmmm (D(2h)(19)) symmetry. This new carbon phase consists of squares C(4), hexagons C(6), and octagons C(8), its dynamical stability is validated based on phonon-mode analysis and it is energetically more favored over previously proposed two-dimensional carbon forms such as net C, planar C(4), biphenylene, graphyne, and the recently prepared graphdiyne. On the other hand, we find that net W possesses strong metallicity due to its rather large density of states across the Fermi level contributed by the carbon p(z) orbital. Through first-principles molecular dynamics simulations, we theoretically demonstrate that selective dehydrogenation of the parallel-laid narrowest angular polycyclic aromatic hydrocarbons (4-AGNRs) would lead to a spontaneous interconversion to such a net W carbon phase, the possible synthetic routes are also addressed. Of particular interest, semiconductivity could be introduced when a net W carbon sheet is cut into ribbons of certain widths. Our work shows that the net W carbon sheet and its nanoribbons have great potential for future nanoelectronics.

Induced ferromagnetism in one-side semihydrogenated silicene and germanene.

The intriguing electronic and magnetic properties of one-side semihydrogenated silicene and germanene are investigated by means of first-principles calculations. Both one-side semihydrogenated silicene and germanene are confirmed as dynamically stable in the ground state based on phonon-mode analysis. Moreover, we find that semihydrogenation from only one side causes localized and unpaired 3p (4p) electrons in the unhydrogenated Si (Ge) sites and then introduces ferromagnetism to silicene (germanene) sheet with no need for doping, cutting, or etching. One-side semihydrogenated silicene and germanene are both identified as semiconductors with direct energy gaps: their gap values obtained from the HSE06 functional are estimated to be 1.74 eV and 1.32 eV, much greater than the PBE-GGA results of 0.94 eV and 0.41 eV, respectively. From pristine to one-side semihydrogenated and then to fully hydrogenated systems, silicene and germanene change from metallic to magnetic semiconducting and then to nonmagnetic semiconducting. The hydrogenation process provides a novel method to tune the properties of silicene and germanene with unprecedented potentials for future nanoelectronics.

Structural stabilities and electronic properties of planar C4 carbon sheet and nanoribbons.

By means of first-principles calculations, we theoretically studied the structural stabilities and electronic properties of a pure-carbon 2D covalent metal named planar C(4) in P4/mmm (D(1)(4h)) symmetry. Planar C(4) is confirmed to be dynamically stable in the ground state based on phonon-mode analysis, and it is more stable than graphyne and the recently prepared graphdiyne. Moreover, it has a higher density of states (DOS) at the Fermi level than any plausible metallic carbon nanotube. Of particular interest, there exist two distinct types of planar C(4) nanoribbons (NRs): type I is predicted to be uniformly metallic regardless of the width change, while type II exhibits remarkable odd-even metal-semiconductor oscillating behavior depending on the width. The edge structure of type II NRs is revealed to be energetically more favored since its formation energy is about 0.45 eV per edge atom lower than that of type I NRs. Our work shows that planar C(4) carbon sheet and its NRs could serve as potential materials for future functional nanodevices.

Selective Sphingosine 1-Phosphate Receptor 1 Modulation Augments Thrombolysis of Low-Dose Tissue Plasminogen Activator Following Cerebrovascular Thrombosis.

Background: Results from our recent study demonstrate that sphingosine-1-phosphate receptor 1 (S1PR1) modulation improves microvascular hemodynamics after cerebrovascular thrombosis. This study was to determine the microvascular hemodynamic effects of a sub-thrombolytic dose of tPA combined with a selective S1PR1 modulator ozanimod in a mouse model of cerebrovascular thrombosis. Methods: Microvascular circulation in mice was monitored in vivo by two-photon microscopy. Thrombosis was induced in cortical arterioles by laser irradiation. Arteriolar flow velocity was measured by line-scanning following plasma-labeling with fluorescein-dextran. Results: Laser-induced thrombosis led to a persistent reduction of flow velocity in cortical arterioles. Sub-thrombolytic dose of tPA along with vehicle control did not improve the flow velocity in cortical arterioles following thrombosis. In contrast, a sub-thrombolytic dose of tPA along with ozanimod dramatically restored flow velocity in cortical arterioles following thrombosis. Ozanimod did not affect coagulation and bleeding time. Notably, ozanimod reduced thrombus volume without altering microvascular lumen diameter. In addition, ozanimod reduced leukocyte components within the thrombus. Conclusions: These findings demonstrate that the thrombolytic effect of a sub-thrombolytic dose of tPA is markedly enhanced by S1PR1 modulation, implying that S1PR1 modulation may improve the therapeutic benefit of low-dose tPA in patients with acute ischemic stroke.

Three-Dimensional Carbon Allotropes Comprising Phenyl Rings and Acetylenic Chains in sp+sp(2) Hybrid Networks.

We here identify by ab initio calculations a new type of three-dimensional (3D) carbon allotropes that consist of phenyl rings connected by linear acetylenic chains in sp+sp(2) bonding networks. These structures are constructed by inserting acetylenic or diacetylenic bonds into an all sp(2)-hybridized rhombohedral polybenzene lattice, and the resulting 3D phenylacetylene and phenyldiacetylene nets comprise a 12-atom and 18-atom rhombohedral primitive unit cells in the symmetry, which are characterized as the 3D chiral crystalline modification of 2D graphyne and graphdiyne, respectively. Simulated phonon spectra reveal that these structures are dynamically stable. Electronic band calculations indicate that phenylacetylene is metallic, while phenyldiacetylene is a semiconductor with an indirect band gap of 0.58 eV. The present results establish a new type of carbon phases and offer insights into their outstanding structural and electronic properties.

Neighbourhood effects on body constitution-A case study of Hong Kong.

Traditional Chinese Medicine (TCM) has long perceived environment as an integral part of the development of body constitution, which is a personal state of health closely related to disease presence. Despite of the ever-growing studies on the clinical effectiveness of TCM and the scientific linking between body constitution and diseases, the geographical influence on body constitution has yet remained an unexplored territory. This study sought to investigate whether the neighbourhood environment is relevant to the composition of body type of a population through statistical multilevel and Geographic Information Systems modelling. The analysis comprised 3277 participants who had completed their body type assessment between 2009 and 2012 inclusive. The multilevel analysis also took simultaneous accounts of both individual-level (gender, age, BMI, type of housing) and area-level (percent greenery, percent road surface, total road intersection, sky view factor, temperature, relative humidity, rainfall and social deprivation index) characteristics to explain geographical variation by body types. Significant random or place effects (p < 0.001) were identified in the multilevel models. The spatial variation of body constitution involved the dynamic interplay between individual and environmental factors. The findings amassed the first scientific indications to back the common belief that place does play a role in the development of body constitution and is worthy of further investigation. By considering spatial and personal attributes simultaneously, the study can yield valuable insights into the patterning of area variation in body constitution and disease presence.

Crystalline structures of polymeric hydrocarbon with 3,4-fold helical chains.

Molecular hydrocarbons are well-known to polymerize under pressure to form covalently bonded frameworks. Here we predict by ab initio calculations two distinct three-dimensional hydrocarbon crystalline structures composed of 3-fold and 4-fold helical CH chains in rhombohedral (R3) and tetragonal (I41/a) symmetry, respectively. Both structures with 1:1 stoichiometry are found to be energetically more favorable than solid acetylene and cubane, and even more stable than benzene II solid at high pressure. The calculations on vibrational, electronic, and optical properties reveal that the new chiral hydrocarbons are dynamically stable with large bulk moduli around 200 GPa, and exhibit a transparent insulating behavior with indirect band gaps of 5.9 ~ 6.7 eV and anisotropic adsorption spectra. Such forms of hydrocarbon, once synthesized, would have wide applications in mechanical, optoelectronic, and biological materials.

Literature review on clinical decision support system reducing medical error.

OBJECTIVES: Quite a number of studies on clinical decision support systems (CDSS) have been published in recent years to assess the characteristics and architecture of CDSS and evaluate the effects of CDSS on clinical work. However, until now there have been no relevant studies to investigate the quantity of these, and their contribution to present day thinking. The aim of this study was to explore the areas of theme, and the study design of research on CDSS in literature published in English and Chinese-language journals. METHODS: We searched the major database including MEDLINE, EMbase, Cochrane Library and four Chinese databases including Chinese Biomedical Literature Database (CBM), Wanfang Data, Chinese Scientific Journal Database (VIP), and Chinese Journals Full-text Database (CNKI) and to analyze the publication years, research themes, authors' affiliations and methodologies of studies. Quality and statistical method were only appraised by classification of study designs. RESULTS: A total of 616 studies published from 1990 to 2013 were included in our research. In the year of 2011 the number of studies reached its peak with 96 studies accounting for 15.58% of the years' publication. We grouped the included studies into six major topic areas of which computerized clinical decision support systems dominated the included studies accounting for 51.46% of all studies. Commentary reviews and cross-sectional studies which took up approximately 46.10% of the included studies, with 30.52% (188 studies) and 15.58% (96 studies) respectively. Most included studies on CDSS were conducted in the following four institutions: universities, hospitals, research institutions and companies. CONCLUSIONS: There is a growing change trend in the number of studies on CDSS research in recent two decades, most of which are non-comparative studies (46.10%) . Only 21 systematic reviews and 22 randomized controlled trails were published with the percentage of 3.41% and 3.57% of the included studies. More methodologically rigorous designs are needed to improve the research quality on CDSS.