Microglia regulate sleep through calcium-dependent modulation of norepinephrine transmission.

Sleep interacts reciprocally with immune system activity, but its specific relationship with microglia-the resident immune cells in the brain-remains poorly understood. Here, we show in mice that microglia can regulate sleep through a mechanism involving Gi-coupled GPCRs, intracellular Ca2+ signaling and suppression of norepinephrine transmission. Chemogenetic activation of microglia Gi signaling strongly promoted sleep, whereas pharmacological blockade of Gi-coupled P2Y12 receptors decreased sleep. Two-photon imaging in the cortex showed that P2Y12-Gi activation elevated microglia intracellular Ca2+, and blockade of this Ca2+ elevation largely abolished the Gi-induced sleep increase. Microglia Ca2+ level also increased at natural wake-to-sleep transitions, caused partly by reduced norepinephrine levels. Furthermore, imaging of norepinephrine with its biosensor in the cortex showed that microglia P2Y12-Gi activation significantly reduced norepinephrine levels, partly by increasing the adenosine concentration. These findings indicate that microglia can regulate sleep through reciprocal interactions with norepinephrine transmission.

Concentric Reversible Visual Field Loss, Nyctalopia, and Dyschromatopsia with Ezetimibe Therapy.

This is a case of ezetimibe-induced concentric field loss, dyschromatopsia, and nyctalopia in a patient with no prior history of retinal dystrophy or drug hypersensitivity. A 55-year-old Caucasian woman presents with a 1-year history of increasing concentric visual field loss, nyctalopia, photophobia, and colour vision impairment. These symptoms correlated with the commencement of ezetimibe therapy 10 mg daily for hypercholesterolaemia. She demonstrated repeatable bilateral visual field constriction on 30-2 Humphrey visual filed testing and colour vision impairment on Ishihara plates (OD: 1/17, OS: 1/17). Biochemical and radiological screening for carcinoma-associated retinopathy was unremarkable. A working diagnosis of drug-induced rod-cone dysfunction was made. Her visual symptoms and field changes completely resolved 3 months after cessation of ezetimibe therapy. This case suggests that ezetimibe is a potential cause of rod-cone dysfunction and should be considered as a differential in patients with new unexplained visual symptoms.

Whole-brain connectivity atlas of glutamatergic and GABAergic neurons in the mouse dorsal and median raphe nuclei.

The dorsal raphe nucleus (DR) and median raphe nucleus (MR) contain populations of glutamatergic and GABAergic neurons that regulate diverse behavioral functions. However, their whole-brain input-output circuits remain incompletely elucidated. We used viral tracing combined with fluorescence micro-optical sectioning tomography to generate a comprehensive whole-brain atlas of inputs and outputs of glutamatergic and GABAergic neurons in the DR and MR. We found that these neurons received inputs from similar upstream brain regions. The glutamatergic and GABAergic neurons in the same raphe nucleus had divergent projection patterns with differences in critical brain regions. Specifically, MR glutamatergic neurons projected to the lateral habenula through multiple pathways. Correlation and cluster analysis revealed that glutamatergic and GABAergic neurons in the same raphe nucleus received heterogeneous inputs and sent different collateral projections. This connectivity atlas further elucidates the anatomical architecture of the raphe nuclei, which could facilitate better understanding of their behavioral functions.

Posterior-only vs. combined posterior-anterior approaches in treating lumbar and lumbosacral spinal tuberculosis: a retrospective study with minimum 7-year follow-up.

BACKGROUND: There is no comparative study with long-term follow-up between posterior-only and combined posterior-anterior approaches in treating lumbar spinal tuberculosis (LSTB) and lumbosacral spinal tuberculosis (LSSTB). This retrospective study aimed to compare and evaluate the long-term outcomes of these two surgical approaches in LSTB and LSSTB. METHODS: Thirty patients with LSTB and 12 patients with LSSTB underwent posterior-only approach (group A); 26 patients with LSTB and 14 patients with LSSTB were managed with combined posterior-anterior approaches (group B). Analysis and comparison in clinical and radiographic outcomes between the two groups were performed. RESULTS: The intra-operative bleeding amount, surgery time, and hospitalization days in group A were less than that in group B (P < 0.05). These patients were followed for a minimum of 7 years. All patients achieved completely healing within 2-year follow-up. Bony fusion was obtained in all patients. The visual analog scale, Japanese Orthopedic Association score, Oswestry Disability index, and Kirkaldy-Willis functional evaluation at the final visit demonstrated that all patients in both groups achieved satisfactory results. There was no significant difference in angle correction or maintaining correction between combined posterior-anterior approaches and posterior-only approach (P > 0.05). Complications occurred in both groups. CONCLUSIONS: Both combined posterior-anterior approaches and posterior-only approach can achieve satisfactory clinical and radiological outcomes of long-term in treating LSTB and LSSTB, while posterior-only approach can safely and effectively achieve lesion debridement, decompression, and stability reconstruction and maintenance with the advantages of less invasive surgery, less bleeding, shorter surgery time, and hospital stay, and fewer complications. So, posterior-only approach seemed to be superior to the combined posterior-anterior one.

One-stage posterior debridement, bone grafting fusion, and mono-segment vs. short-segment fixation for single-segment lumbar spinal tuberculosis: minimum 5-year follow-up outcomes.

BACKGROUND: To compare the clinical and radiological outcomes between posterior mono-segment and short-segment fixation combined with one-stage posterior debridement and bone grafting fusion in treating single-segment lumbar spinal tuberculosis (LSTB). METHODS: Sixty-two patients with single-segment LSTB treated by a posterior-only approach were divided into two groups: short-segment fixation (Group A, n = 32) and mono-segment fixation (Group B, n = 30). The clinical and radiographic outcomes were analyzed and compared between the two groups. RESULTS: The intraoperative bleeding volume, operation time, and hospitalization duration were lower in Group B than in Group A. All patients achieved the bony fusion criteria. The visual analog scale score, Japanese Orthopedic Association score, and Oswestry Disability Index were substantially improved 3 months postoperatively and at the last visit in both groups, with no significant difference between the two groups (P > 0.05). Kirkaldy-Willis functional evaluation at the final follow-up demonstrated that all patients in both groups achieved excellent or good results. The difference in the angle correction rate and correction loss between Groups A and B was not significant (P > 0.05). CONCLUSIONS: One-stage posterior debridement, bone grafting fusion, and mono-segment or short-segment fixation can provide satisfactory clinical and radiological outcomes. Mono-segment fixation is more suitable for the treatment of single-segment LSTB because the lumbar segments with normal motion can be preserved with less trauma, a shorter operation time, shorter hospitalization, and lower costs.

Treatment of Monosegment Spinal Tuberculosis via Posterior Unilateral Vertebral Lamina Fenestration Debridement and Bone Grafting Fusion Combined with Laminar Reconstruction and Internal Fixation: A Retrospective Case-Control Study with a Minimum 5-Year Follow-Up.

OBJECTIVE: To investigate the clinical and imaging outcomes of posterior unilateral vertebral lamina fenestration debridement and bone grafting fusion combined with laminar reconstruction and instrumentation compared with the traditional posterior-only method for treating monosegment spinal tuberculosis. METHODS: Fifty-four patients underwent posterior unilateral vertebral lamina fenestration debridement and bone grafting fusion combined with laminar reconstruction and internal fixation (group A), and 60 patients underwent 1-stage posterior debridement, laminectomy decompression, bone grafting fusion and instrumentation (group B). The clinical and radiographic outcomes of these groups were analyzed and compared. RESULTS: Group A had less intraoperative blood loss, shorter hospitalization, and a shorter fusion time than did group B (P < 0.05). At 3 months postoperatively, group A had a lower mean Oswestry Disability Index than did group B (P < 0.05). At the final follow-up, group A had a lower mean visual analog scale pain score and a lower mean ODI than did group B (P < 0.05). Group A had a smaller kyphotic angle loss (1.2° ± 0.6°) and loss rate (4.8% ± 2.5%) than did group B (P < 0.05). CONCLUSIONS: The procedure of posterior unilateral vertebral lamina fenestration debridement and bone grafting fusion combined with laminar reconstruction and internal fixation is safe and effective in treating monosegment spinal tuberculosis. Compared with the conventional posterior-only approach, this method maximizes the retention and reconstruction of the posterior column and is minimally invasive, achieving faster postoperative recovery with fewer complications.

Pinpointing Morphology and Projection of Excitatory Neurons in Mouse Visual Cortex.

The excitatory neurons in the visual cortex are of great significance for us in understanding brain functions. However, the diverse neuron types and their morphological properties have not been fully deciphered. In this paper, we applied the brain-wide positioning system (BPS) to image the entire brain of two Thy1-eYFP H-line male mice at 0.2 µm × 0.2 µm × 1 µm voxel resolution. A total of 103 neurons were reconstructed in layers 5 and 6 of the visual cortex with single-axon-level resolution. Based on the complete topology of neurons and the inherent positioning function of the imaging method, we classified the observed neurons into six types according to their apical dendrites and somata location: star pyramidal cells in layer 5 (L5-sp), slender-tufted pyramidal cells in layer 5 (L5-st), tufted pyramidal cells in layer 5 (L5-tt), spiny stellate-like cells in layer 6 (L6-ss), star pyramidal cells in layer 6 (L6-sp), and slender-tufted pyramidal cells in layer 6 (L6-st). By examining the axonal projection patterns of individual neurons, they can be categorized into three modes: ipsilateral circuit connection neurons, callosal projection neurons and corticofugal projection neurons. Correlating the two types of classifications, we have found that there are at least two projection modes comprised in the former defined neuron types except for L5-tt. On the other hand, each projection mode may consist of four dendritic types defined in this study. The axon projection mode only partially correlates with the apical dendrite feature. This work has demonstrated a paradigm for resolving the visual cortex through single-neuron-level quantification and has shown potential to be extended to reveal the connectome of other defined sensory and motor systems.

Whole Brain Mapping of Long-Range Direct Input to Glutamatergic and GABAergic Neurons in Motor Cortex.

Long-range neuronal circuits play an important role in motor and sensory information processing. Determining direct synaptic inputs of excited and inhibited neurons is important for understanding the circuit mechanisms involved in regulating movement. Here, we used the monosynaptic rabies tracing technique, combined with fluorescent micro-optical sectional tomography, to characterize the brain-wide input to the motor cortex (MC). The whole brain dataset showed that the main excited and inhibited neurons in the MC received inputs from similar brain regions with a quantitative difference. With 3D reconstruction we found that the distribution of input neurons, that target the primary and secondary MC, had different patterns. In the cortex, the neurons projecting to the primary MC mainly distributed in the lateral and anterior portion, while those to the secondary MC distributed in the medial and posterior portion. The input neurons in the subcortical areas also showed the topographic shift model, as in the thalamus, the neurons distributed as outer and inner shells while the neurons in the claustrum and amygdala were in the ventral and dorsal part, respectively. These results lay the anatomical foundation to understanding the organized pattern of motor circuits and the functional differences between the primary and secondary MC.

Genetic Single Neuron Anatomy Reveals Fine Granularity of Cortical Axo-Axonic Cells.

Parsing diverse nerve cells into biological types is necessary for understanding neural circuit organization. Morphology is an intuitive criterion for neuronal classification and a proxy of connectivity, but morphological diversity and variability often preclude resolving the granularity of neuron types. Combining genetic labeling with high-resolution, large-volume light microscopy, we established a single neuron anatomy platform that resolves, registers, and quantifies complete neuron morphologies in the mouse brain. We discovered that cortical axo-axonic cells (AACs), a cardinal GABAergic interneuron type that controls pyramidal neuron (PyN) spiking at axon initial segments, consist of multiple subtypes distinguished by highly laminar-specific soma position and dendritic and axonal arborization patterns. Whereas the laminar arrangements of AAC dendrites reflect differential recruitment by input streams, the laminar distribution and local geometry of AAC axons enable differential innervation of PyN ensembles. This platform will facilitate genetically targeted, high-resolution, and scalable single neuron anatomy in the mouse brain.

Synthesis of Superparamagnetic Core-Shell Structure Supported Pd Nanocatalysts for Catalytic Nitrite Reduction with Enhanced Activity, No Detection of Undesirable Product of Ammonium, and Easy Magnetic Separation Capability.

Superparamagnetic nanocatalysts could minimize both the external and internal mass transport limitations and neutralize OH(-) produced in the reaction more effectively to enhance the catalytic nitrite reduction efficiency with the depressed product selectivity to undesirable ammonium, while possess an easy magnetic separation capability. However, commonly used qusi-monodispersed superparamagnetic Fe3O4 nanosphere is not suitable as catalyst support for nitrite reduction because it could reduce the catalytic reaction efficiency and the product selectivity to N2, and the iron leakage could bring secondary contamination to the treated water. In this study, protective shells of SiO2, polymethylacrylic acid, and carbon were introduced to synthesize Fe3O4@SiO2/Pd, Fe3O4@PMAA/Pd, and Fe3O4@C/Pd catalysts for catalytic nitrite reduction. It was found that SiO2 shell could provide the complete protection to Fe3O4 nanosphere core among these shells. Because of its good dispersion, dense structure, and complete protection to Fe3O4, the Fe3O4@SiO2/Pd catalyst demonstrated the highest catalytic nitrite reduction activity without the detection of NH4(+) produced. Due to this unique structure, the activity of Fe3O4@SiO2/Pd catalysts for nitrite reduction was found to be independent of the Pd nanoparticle size or shape, and their product selectivity was independent of the Pd nanoparticle size, shape, and content. Furthermore, their superparamagnetic nature and high saturation magnetization allowed their easy magnetic separation from treated water, and they also demonstrated a good stability during the subsequent recycling experiment.

Synthesis of Mn3O4/CeO2 Hybrid Nanotubes and Their Spontaneous Formation of a Paper-like, Free-Standing Membrane for the Removal of Arsenite from Water.

One-dimensional nanomaterials may organize into macrostructures to have hierarchically porous structures, which could not only be easily adopted into various water treatment apparatus to solve the separation issue of nanomaterials from water but also take full advantage of their nanosize effect for enhanced water treatment performance. In this work, a novel template-based process was developed to create Mn3O4/CeO2 hybrid nanotubes, in which a redox reaction happened between the OMS-2 nanowire template and Ce(NO3)3 to create hybrid nanotubes without the template removal process. Both the Ce/Mn ratio and the precipitation agent were found to be critical in the formation of Mn3O4/CeO2 hybrid nanotubes. Because of their relatively large specific surface area, porous structure, high pore volume, and proper surface properties, these Mn3O4/CeO2 hybrid nanotubes demonstrated good As(III) removal performances in water. These Mn3O4/CeO2 hybrid nanotubes could form paper-like, free-standing membranes spontaneously by a self-assembly process without high temperature treatment, which kept the preferable properties of Mn3O4/CeO2 hybrid nanotubes while avoiding the potential nanomaterial dispersion problem. Thus, they could be readily utilized in commonly used flow-through reactors for water treatment purposes. This approach could be further applied to other material systems to create various hybrid nanotubes for a broad range of technical applications.

Synthesis of tin oxide nanospheres under ambient conditions and their strong adsorption of As(III) from water.

The development of highly efficient As(iii) adsorbents is critical to largely simplify the arsenic treatment process and lower its cost. For the first time, SnO2 nanospheres were demonstrated to possess a highly efficient As(iii) adsorption capability from water in a near neutral pH environment as predicted by the material criterion we recently developed for the selection of highly efficient arsenic adsorbents. These SnO2 nanospheres were synthesized by a simple and cost-effective hydrolysis process with the assistance of ethyl acetate under ambient conditions, which had a good dispersity, a narrow size distribution, a relatively large specific surface area, and a porous structure. A fast As(iii) adsorption was observed in the kinetics study on these SnO2 nanospheres, and their Langmuir adsorption capacity was determined to be ∼112.7 mg g(-1) at pH ∼7. The As(iii) adsorption mechanism on SnO2 nanospheres was examined by both macroscopic and microscopic techniques, which demonstrated that it followed the inner-sphere complex model. These SnO2 nanospheres demonstrated effective As(iii) adsorption even with exceptionally high concentrations of co-existing ions, and a good regeneration capability by washing with NaOH solution.

As(III) removal by hydrous titanium dioxide prepared from one-step hydrolysis of aqueous TiCl(4) solution.

Hydrous titanium dioxide (TiO(2)·xH(2)O) nanoparticles were synthesized by a low-cost one-step hydrolysis process with aqueous TiCl(4) solution. These TiO(2)·xH(2)O nanoparticles ranged from 3 to 8 nm and formed aggregates with a highly porous structure, resulting in a large surface area and easy removal capability from aqueous environment after the treatment. Their effectiveness on the removal of As(III) (arsenite) from water was investigated in both laboratory and natural water samples. The adsorption capacity on As(III) of these TiO(2)·xH(2)O nanoparticles reached over 83 mg/g at near neutral pH environment, and over 96 mg/g at pH 9.0. Testing with a As(III) contaminated natural lake water sample confirmed the effectiveness of these TiO(2)·xH(2)O nanoparticles in removing As(III) from natural water. The high adsorption capacity of the TiO(2)·xH(2)O nanoparticles is related to the high surface area, large pore volume, and the presence of high affinity surface hydroxyl groups.

[Analysis of protein interaction network and function of Staphylococcus aureus].

OBJECTIVE: Staphylococcus aureus is a member of Gram positive bacteria,but is also one of common pathogens that are most difficult to treat. It infects human skin, soft tissue, mucous membrane, bone and joint, especially in the nosocomial environment. Because studies on Staphylococcus aureus before were largely based on a single gene or protein, it is necessary to study this organism from the whole genome. METHODS: We used bioinformatics methods including five computational methods (phylogenetic profile, gene neighbor method, operon method, gene fusion method, interolog) to predict the protein interaction network of Staphylococcus aureus. RESULTS: We constructed the protein interaction network of Staphylococcus aureus and studied its function. CONCLUSION: Through the network analysis, we found that the protein interaction network of Staphylococcus aureus was subject to scale-free property and a number of very important proteins, such as SA0939, SA0868, rpID. Through the analysis of the important cell wall synthesis and signal transduction and regulation local networks, we also found some very important proteins. Such information will help us better understand pathogenic mechanism and develop new drug targets of Staphylococcus aureus.