Gut microbiome promotes mice recovery from stress-induced depression by rescuing hippocampal neurogenesis.

Studies from rodents to primates and humans indicate that individuals vary in how resilient they are to stress, and understanding the basis of these variations may help improve treatments for depression. Here we explored the potential contribution of the gut microbiome to such variation. Mice were exposed to chronic unpredictable mild stress (CUMS) for 4 weeks then allowed to recover for 3 weeks, after which they were subjected to behavioral tests and categorized as showing low or high stress resilience. The two types of mouse were compared in terms of hippocampal gene expression using RNA sequencing, fecal microbiomes using 16S RNA sequencing, and extent of neurogenesis in the hippocampus using immunostaining of brain sections. Fecal microbiota were transplanted from either type of mouse into previously stress-exposed and stress-naïve animals, and the effects of the transplantation on stress-induced behaviors and neurogenesis in the hippocampus were examined. Finally, we blocked neurogenesis using temozolomide to explore the role of neurogenesis promoted by fecal microbiota transplantation in enhancing resilience to stress. Results showed that highly stress-resilient mice, but not those with low resilience, improved significantly on measures of anhedonia, behavioral despair, and anxiety after 3-week recovery from CUMS. Their feces showed greater abundance of Lactobacillus, Bifidobacterium and Romboutsia than feces from mice with low stress resilience, as well as lower abundance of Staphylococcus, Psychrobacter and Corynebacterium. Similarly, highly stress-resilient mice showed greater neurogenesis in hippocampus than animals with low stress resilience. Transplanting fecal microbiota from mice with high stress resilience into previously CUMS-exposed recipients rescued neurogenesis in hippocampus, facilitating recovery from stress-induced depression and cognitive decline. Blockade of neurogenesis with temozolomide abolished recovery of recipients from CUMS-induced depression and cognitive decline in mice transplanted with fecal microbiota from mice with high stress resilience. In conclusion, our results suggested that remodeling of the gut microbiome after stress may reverse stress-induced impairment of hippocampal neurogenesis and thereby promote recovery from stress-induced depression.

Priming of microglia with dysfunctional gut microbiota impairs hippocampal neurogenesis and fosters stress vulnerability of mice.

BACKGROUND: Mental disorders may be involved in neuroinflammatory processes that are triggered by gut microbiota. How gut microbiota influence microglia-mediated sensitivity to stress remains unclear. Here we explored in an animal model of depression whether disruption of the gut microbiome primes hippocampal microglia, thereby impairing neurogenesis and sensitizing to stress. METHODS: Male C57BL/6J mice were exposed to chronic unpredictable mild stress (CUMS) for 4 weeks, and effects on gut microbiota were assessed using 16S rRNA sequencing. Fecal microbiota was transplanted from control or CUMS mice into naïve animals. The depression-like behaviors of recipients were evaluated in a forced swimming test and sucrose preference test. The morphology and phenotype of microglia in the hippocampus of recipients were examined using immunohistochemistry, quantitative PCR, and enzyme-linked immunosorbent assays. The recipients were treated with lipopolysaccharide or chronic stress exposure, and effects were evaluated on behavior, microglial responses and hippocampal neurogenesis. Finally, we explored the ability of minocycline to reverse the effects of CUMS on hippocampal neurogenesis and stress sensitivity in recipients. RESULTS: CUMS altered the gut microbiome, leading to higher relative abundance of some bacteria (Helicobacter, Bacteroides, and Desulfovibrio) and lower relative abundance of some bacteria (Lactobacillus, Bifidobacterium, and Akkermansia). Fecal microbiota transplantation from CUMS mice to naïve animals induced microglial priming in the dentate gyrus of recipients. This microglia showed hyper-ramified morphology, and became more sensitive to LPS challenge or chronic stress, which characterized by more significant morphological changes and inflammatory responses, as well as impaired hippocampal neurogenesis and increased depressive-like behaviors. Giving minocycline to recipients reversed these effects of fecal transplantation. CONCLUSIONS: These findings suggest that gut microbiota from stressed animals can induce microglial priming in the dentate gyrus, which is associated with a hyper-immune response to stress and impaired hippocampal neurogenesis. Remodeling the gut microbiome or inhibiting microglial priming may be strategies to reduce sensitivity to stress.

Different Doses of Oxycodone for Endoscopic Injection Sclerotherapy of Esophageal Varices.

BACKGROUND The aim of the present study was to evaluate the effects of different doses of oxycodone during endoscopic injection sclerotherapy (EIS) for esophageal varices with painless sclerosing agents. MATERIAL AND METHODS A total of 119 patients were randomly divided into 3 groups: Group A, midazolam and 0.075 mg/kg oxycodone (n=40); Group B, midazolam and 0.1 mg/kg oxycodone (n=40); and Group C, midazolam and 0.125 mg/kg oxycodone (n=39). The main observation index was the incidence of body movement during the perioperative period. The secondary indices were additional propofol usage; postoperative analgesic usage; other adverse effects, such as hypoxia, myoclonus, and cough; and satisfaction scores for surgeons and patients. RESULTS The incidence rates for body movement during the perioperative period in groups A, B, and C were 33%, 13%, and 0, respectively (P<0.001). The satisfaction scores for surgeons and patients were highest in Group C (0.125 mg/kg oxycodone). The incidence rates for hypoxia before EIS were 15%, 8%, and 33% (P=0.026) and during EIS were 23%, 3%, and 0% (P<0.001), respectively. There were no significant between-group differences with respect to other adverse effects. CONCLUSIONS The ideal dose of oxycodone for perioperative analgesia during EIS for esophageal varices is 0.125 mg/kg.

Priming of microglia with IFN-γ impairs adult hippocampal neurogenesis and leads to depression-like behaviors and cognitive defects.

Neuroinflammation driven by interferon-gamma (IFN-γ) and microglial activation has been linked to neurological disease. However, the effects of IFN-γ-activated microglia on hippocampal neurogenesis and behavior are unclear. In the present study, IFN-γ was administered to mice via intracerebroventricular injection. Mice received intraperitoneal injection of ruxolitinib to inhibit the JAK/STAT1 pathway or injection of minocycline to inhibit microglial activation. During a 7-day period, mice were assessed for depressive-like behaviors and cognitive impairment based on a series of behavioral analyses. Effects of the activated microglia on neural stem/precursor cells (NSPCs) were examined, as was pro-inflammatory cytokine expression by activated microglia. We showed that IFN-γ-injected animals showed long-term adult hippocampal neurogenesis reduction, behavior despair, anhedonia, and cognitive impairment. Chronic activation with IFN-γ induces reactive phenotypes in microglia associated with morphological changes, population expansion, MHC II and CD68 up-regulation, and pro-inflammatory cytokine (IL-1ß, TNF-α, IL-6) and nitric oxide (NO) release. Microglia isolated from the hippocampus of IFN-γ-injected mice suppressed NSPCs proliferation and stimulated apoptosis of immature neurons. Inhibiting of the JAK/STAT1 pathway in IFN-γ-injected animals to block microglial activation suppressed microglia-mediated neuroinflammation and neurogenic injury, and alleviated depressive-like behaviors and cognitive impairment. Collectively, these findings suggested that priming of microglia with IFN-γ impairs adult hippocampal neurogenesis and leads to depression-like behaviors and cognitive defects. Targeting microglia by modulating levels of IFN-γ the brain may be a therapeutic strategy for neurodegenerative diseases and psychiatric disorders.

Acoustic Shadowing Facilitates Ultrasound-guided Radial Artery Cannulation in Young Children.

BACKGROUND: Arterial cannulation in young children can be challenging. Ultrasound guidance using focused acoustic shadowing may be suitable for guiding radial artery puncture in young children. The present research tested the hypothesis that ultrasound guidance using focused acoustic shadowing helps increase the success rate of radial artery cannulation in this population. METHODS: In a double-blinded, parallel-group trial, 79 young children undergoing surgery under general anesthesia were randomly assigned to two groups (1:1 ratio): the traditional ultrasound group and the novel ultrasound group. Young children in the traditional group underwent conventional ultrasound-guided radial artery puncture, whereas those in the novel ultrasound group underwent radial artery puncture guided by acoustic shadowing ultrasound with double developing lines. All radial artery punctures were performed using the short-axis out-of-plane approach. The primary endpoint was the success rate of cannulation at the first attempt. The secondary endpoints included cannulation failure rate, ultrasound location time, and puncture time. RESULTS: The success rate of cannulation at the first attempt in the novel ultrasound group (35 of 39 [90%]) was significantly higher than that in the traditional ultrasound group (24 of 40 [60%]; difference: 30% [95% CI, 12 to 48%], P =0.002). None of the patients in the ultrasound with acoustic shadowing group experienced failure of radial artery puncture and cannulation. The ultrasound location time and puncture time in the ultrasound acoustic shadowing group were significantly lower than that in the traditional ultrasound group (location time: median [interquartile range]: 6 [5, 8] vs. 18 [15, 21] s; puncture time: 24 [15, 41] vs. 40 [23, 56] s). CONCLUSIONS: Acoustic shadowing via the use of double developing lines significantly improved the success rate of radial artery puncture in young children, compared with that achieved with the use of traditional ultrasound guidance.

Application of Optimized Ultrasonic Localization System for Radial Artery Puncture by Intern Doctors: A Randomized Trial.

BACKGROUND Ultrasound with developing line may by suitable for medical personnel who are inexperienced in the use of ultrasound-guided radial artery puncture. In this trial, we assessed whether this technology could increase the success rate of radial artery puncture performed by interns. MATERIAL AND METHODS Seventy-seven patients undergoing general anesthesia were enrolled and randomly divided into 2 groups: an ultrasound with developing line group and a traditional ultrasound group. All radial artery punctures were performed by interns who received theoretical explanation (including video demonstration of puncture) and on-site guidance puncture once. The primary end-point was the success rate of cannulation at the first attempt and the secondary end-point was cannulation failure rate. RESULTS The success rate of cannulation at the first attempt in ultrasound in the developing line group was significantly higher than that in the traditional ultrasound group (proportion difference: 34.21%, 95% confidence interval [CI], -0.5483 to -0.1334; P=0.0025). However, no significant between-group difference was observed with respect to failure rate (mean difference 95% CI, (-0.0084 to 0.2743; P=0.0866). The ultrasonic location time in the ultrasound with developing line group was significantly lower than that in the traditional ultrasound group (mean difference -12.4 seconds, 95% CI, 10.64 to 13.98 s; P<0.0000). CONCLUSIONS Use of ultrasound with developing line significantly improved the success rate of radial artery puncture performed by interns as compared to that with use of traditional dynamic ultrasound guidance technology.

Analgesic Effects of Oxycodone Relative to Those of Sufentanil, in the Presence of Midazolam, During Endoscopic Injection Sclerotherapy for Patients With Cirrhosis and Esophageal Varices.

BACKGROUND: We evaluated the efficacy and gastroenterologist/patient satisfaction of midazolam combined with oxycodone, relative to that of midazolam combined with sufentanil, for anesthesia during endoscopic injection sclerotherapy (EIS) in patients with cirrhosis and esophageal varices. METHODS: Patients with cirrhosis (20-69 years of age), body mass index, 18-25 kg/m, American Society of Anesthesiology patient classification physical status I-II who underwent elective EIS were randomly assigned to 1 of 2 groups. In this prospective, double-blinded, randomized controlled trial, 1 group received midazolam and oxycodone (n = 64), and the other group received midazolam and sufentanil (n = 63). Primary and secondary outcome measures were compared between groups. The primary outcome measure was the incidence of hypoxia. Secondary outcome measures included perioperative limb movement, need for rescue analgesics, need for additional sedative propofol, specified adverse reactions (postoperative myoclonus, nausea, vomiting, dizziness, and drowsiness), gastroenterologist satisfaction, and patient satisfaction with postoperative analgesia. RESULTS: Patients in the midazolam-oxycodone group had 32% fewer episodes of hypoxia than did those in the midazolam-sufentanil group (95% confidence interval [CI], -45% to -18%; P < .001), 36.73% fewer perioperative limb movements (95% CI, -51.73% to -21.73%; P < .001), 19.12% fewer required rescue analgesics (95% CI, -30.85% to -7.40%; P = .002), and less propofol requirement in the perioperative period (before EIS, -17.83%; 95% CI, -33.82% to -1.85%; P = .003; throughout EIS, -36.73%; 95% CI, -51.73% to -21.73%; P < .001). The incidence rates for adverse reactions were similar between groups. Both the gastroenterologist and patients reported higher degrees of satisfaction with oxycodone than with sufentanil. CONCLUSIONS: Oxycodone in combination with midazolam may provide an anesthetic technique that results in fewer episodes of hypoxia and other adverse conditions during EIS.

Constructing Three-Dimensional Mesoporous Bouquet-Posy-like TiO2 Superstructures with Radially Oriented Mesochannels and Single-Crystal Walls.

Constructing three-dimensional (3-D) hierarchical mesostructures with unique morphology, pore orientation, single-crystal nature, and functionality remains a great challenge in materials science. Here, we report a confined microemulsion self-assembly approach to synthesize an unprecedented type of 3-D highly ordered mesoporous TiO2 superstructure (Level-1), which consists of 1 spherical core and 12 symmetric satellite hemispheres epitaxially growing out of the core vertices. A more complex and asymmetric TiO2 superstructure (Level-2) with 13 spherical cores and up to 44 symmetric satellite hemispheres can also be well manipulated by increasing the size or content of impregnated TiO2 precursor emulsion droplets. The obtained 3-D mesoporous TiO2 superstructures have well-defined bouquet-posy-like topologies, oriented hexagonal mesochannels, high accessible surface area (134-148 m2/g), large pore volume (0.48-0.51 cm3/g), and well single-crystalline anatase walls with dominant (001) active facets. More interestingly, all cylindrical mesopore channels are highly interconnected and radially distributed within the whole superstructures, and all TiO2 nanocrystal building blocks are oriented grown into a single-crystal anatase wall, making them ideal candidates for various applications ranging from catalysis to optoelectronics. As expected, the bouquet-posy-like mesoporous TiO2 superstructure supported catalysts show excellent catalytic activity (≥99.7%) and selectivity (≥96%) in cis-semihydrogenation of various alkynes, exceeding that of commercial TiO2 (P25) supported catalyst by a factor of 10. No decay in the activity was observed for 25 cycles, revealing a high stability of the mesoporous TiO2 superstructure supported catalyst.

Direct Superassemblies of Freestanding Metal-Carbon Frameworks Featuring Reversible Crystalline-Phase Transformation for Electrochemical Sodium Storage.

High-power sodium-ion batteries (SIBs) with long-term cycling attract increasing attention for large-scale energy storage. However, traditional SIBs toward practical applications still suffer from low rate capability and poor cycle induced by pulverization and amorphorization of anodes at high rate (over 5 C) during the fast ion insertion/extraction process. The present work demonstrates a robust strategy for a variety of (Sb-C, Bi-C, Sn-C, Ge-C, Sb-Bi-C) freestanding metal-carbon framework thin films via a space-confined superassembly (SCSA) strategy. The sodium-ion battery employing the Sb-C framework exhibits an unprecedented performance with a high specific capacity of 246 mAh g-1, long life cycle (5000 cycles), and superb capacity retention (almost 100%) at a high rate of 7.5 C (3.51A g-1). Further investigation indicates that the unique framework structure enables unusual reversible crystalline-phase transformation, guaranteeing the fast and long-cyclability sodium storage. This study may open an avenue to developing long-cycle-life and high-power SIBs for practical energy applications.

Counting and dynamic studies of the small unilamellar phospholipid vesicle translocation with single conical glass nanopores.

Phospholipid vesicles are ubiquitous cellular organelles that perform vital functions including materials transport and information transmission and have found promising biomedical applications. Although the transmembrane translocation (via nanopores) of phospholipid vesicles, especially small unilamellar phospholipid vesicles (SUVs), is recognized to be very important for these processes and applications, the details and dynamics remain not very clear. Herein, we use single conical glass nanopores as a model platform to systematically investigate the translocation dynamics of SUVs (∼50-60 nm in diameter) through small nanopores with orifice diameters ranging from ∼14 to 72 nm. Dynamic translocation of individual SUVs one by one through the nanopores was clearly observed and was analyzed by the occurrence of periodic oscillation in ionic current blockage signal under a negatively applied voltage. Translocation behaviors of the SUVs, in terms of magnitude and duration of ionic current blockage signal, varied and can be modulated by changing nanopore size, solution pH, vesicle concentration, applied voltage, and inner surface charge properties of the nanopores. The translocation rate of the SUVs through an ∼72 nm nanopore is typically on a time scale of a few seconds (per SUV translocation event) and found nonlinearly proportional to the concentration of the SUVs. Moreover, the electrophoretic force has been verified as a main force to drive the SUVs through the nanopore since there is a nearly linear relationship between the current blockage frequency of SUVs translocation and the applied bias potentials ranging from -0.6 to -1 V. The findings provide fundamental insights into the translocation and interactions of SUVs with nanopores, and the reported nanopore platform may find potential useful bioapplications in single-cell and single-vesicle studies.

Facile one-step photochemical fabrication and characterization of an ultrathin gold-decorated single glass nanopipette.

The inner surface of a conical glass nanopipette was modified with ultrathin gold film by a facile one-step photochemical approach, using HAuCl4 and ethanol as common reagents with the aid of UV irradiation. The method is simple, straightforward, time-saving, and environmentally friendly. The morphology and component of the as-prepared ultrathin gold film was thoroughly characterized by transmission electron microscopy (TEM), energy-dispersive X-ray (EDX) analysis, and X-ray photoelectron spectroscopy (XPS). The mechanism of the gold film growth was briefly discussed. Other small photochemical reagents with a hydroxy group, e.g., ethylene glycol, methanol, and glucose, may also work but with a different rate of reaction. The facile ultrathin gold decoration of a single glass nanopipette renders the glass nanopipette-based nanopore platform very easy for surface chemical modifications and potential sensing applications. The success of the gold decoration on the inner surface of the glass nanopore was further confirmed electrochemically by surface modification of a small thiol molecule (cysteine), and the pH (surface charge)-dependent ionic current rectification behaviors through the nanopore were investigated. Due to its facile preparation, the method and the Au-decorated glass nanopore would find promising and extended applications in ultrasensitive detection and biosensing.

Smart Plasmonic Glucose Nanosensors as Generic Theranostic Agents for Targeting-Free Cancer Cell Screening and Killing.

Fast and accurate identification of cancer cells from healthy normal cells in a simple, generic way is very crucial for early cancer detection and treatment. Although functional nanoparticles, like fluorescent quantum dots and plasmonic Au nanoparticles (NPs), have been successfully applied for cancer cell imaging and photothermal therapy, they suffer from the main drawback of needing time-consuming targeting preparation for specific cancer cell detection and selective ablation. The lack of a generic and effective method therefore limits their potential high-throughput cancer cell preliminary screening and theranostic applications. We report herein a generic in vitro method for fast, targeting-free (avoiding time-consuming preparations of targeting moiety for specific cancer cells) visual screening and selective killing of cancer cells from normal cells, by using glucose-responsive/-sensitive glucose oxidase-modified Ag/Au nanoshells (Ag/Au-GOx NSs) as a smart plasmonic theranostic agent. The method is generic to some extent since it is based on the distinct localized surface plasmon resonance (LSPR) responses (and colors) of the smart nanoprobe with cancer cells (typically have a higher glucose uptake level) and normal cells.

Wet-chemical enzymatic preparation and characterization of ultrathin gold-decorated single glass nanopore.

The conical glass nanopore was modified through layer-by-layer electrostatic deposition of a monolayer of glucose oxidase, and then an ultrathin gold film was formed in situ through enzyme-catalyzed reactions. The morphology and components of single glass nanopore before and after ultrathin Au deposition were characterized by transmission electron microscopy (TEM) and energy-dispersive X-ray (EDX) analysis, respectively. In particular, the quenching of the quantum dots fluorescence in the nanopore tip zone further illustrated that the gold nanofilm was successfully deposited on the inner wall of the single glass nanopore. The Au thin films make the glass nanopores more biologically friendly and allow the nanopores facile functionalization of the surface through the Au-S bonds. For instance, the ionic current rectification (ICR) properties of the gold-decorated glass nanopores could be switched readily at different pHs by introducing different thiol molecules.

Ionic liquid-functionalized fluorescent carbon nanodots and their applications in electrocatalysis, biosensing, and cell imaging.

In this article, ionic liquid-functionalized carbon nanodots (IL-CDs) were produced in a simple manner by electrochemical exfoliation of graphite rods in the presence of an amino-terminated ionic liquid, and their preliminary applications were exploited. TEM and AFM results showed that these IL-CDs are about 2.6 nm in diameter. The small-sized IL-CDs have strong photoluminescence, with a quantum yield of about 11.3%, and could be used for cell imaging. Moreover, the IL-CDs exhibit good electron transfer properties and catalytic activities for O2 and H2O2 reduction. Additionally, the as-prepared IL-CDs can be applied as a matrix for immobilizing enzymes (glucose oxidase) to construct biosensors. Due to these favorable properties, IL-CDs will find promising practical applications in electrocatalysis, biosensing, and bioimaging.

Gut microbiota regulate stress resistance by influencing microglia-neuron interactions in the hippocampus.

Communication among the brain, gut and microbiota in the gut is known to affect the susceptibility to stress, but the mechanisms involved are unclear. Here we demonstrated that stress resistance in mice was associated with more abundant Lactobacillus and Akkermansia in the gut, but less abundant Bacteroides, Alloprevotella, Helicobacter, Lachnoclostridium, Blautia, Roseburia, Colidextibacter and Lachnospiraceae NK4A136. Stress-sensitive animals showed higher permeability and stronger immune responses in their colon, as well as higher levels of pro-inflammatory cytokines in serum. Their hippocampus also showed more extensive microglial activation, abnormal interactions between microglia and neurons, and lower synaptic plasticity. Transplanting fecal microbiota from stress-sensitive mice into naïve ones perturbed microglia-neuron interactions and impaired synaptic plasticity in the hippocampus, translating to more depression-like behavior after stress exposure. Conversely, transplanting fecal microbiota from stress-resistant mice into naïve ones protected microglia from activation and preserved synaptic plasticity in the hippocampus, leading to less depression-like behavior after stress exposure. These results suggested that gut microbiota may influence resilience to chronic psychological stress by regulating microglia-neuron interactions in the hippocampus.

Priming of hippocampal microglia by IFN-γ/STAT1 pathway impairs social memory in mice.

Social behavior is inextricably linked to the immune system. Although IFN-γ is known to be involved in social behavior, yet whether and how it encodes social memory remains unclear. In the current study, we injected with IFN-γ into the lateral ventricle of male C57BL/6J mice, and three-chamber social test was used to examine the effects of IFN-γ on their social preference and social memory. The morphology of microglia in the hippocampus, prelimbic cortex and amygdala was examined using immunohistochemistry, and the phenotype of microglia were examined using immunohistochemistry and enzyme-linked immunosorbent assays. The IFN-γ-injected mice were treated with lipopolysaccharide, and effects of IFN-γ on behavior and microglial responses were evaluated. STAT1 pathway and microglia-neuron interactions were examined in vivo or in vitro using western blotting and immunohistochemistry. Finally, we use STAT1 inhibitor or minocycline to evaluated the role of STAT1 in mediating the microglial priming and effects of primed microglia in IFN-γ-induced social dysfunction. We demonstrated that 500 ng of IFN-γ injection results in significant decrease in social index and social novelty recognition index, and induces microglial priming in hippocampus, characterized by enlarged cell bodies, shortened branches, increased expression of CD68, CD86, CD74, CD11b, CD11c, CD47, IL-33, IL-1ß, IL-6 and iNOS, and decreased expression of MCR1, Arg-1, IGF-1 and BDNF. This microglia subpopulation is more sensitive to LPS challenge, which characterized by more significant morphological changes and inflammatory responses, as well as induced increased sickness behaviors in mice. IFN-γ upregulated pSTAT1 and STAT1 and promoted the nuclear translocation of STAT1 in the hippocampal microglia and in the primary microglia. Giving minocycline or STAT1 inhibitor fludarabin blocked the priming of hippocampal microglia induced by IFN-γ, ameliorated the dysfunction in hippocampal microglia-neuron interactions and synapse pruning by microglia, thereby improving social memory deficits in IFN-γ injected mice. IFN-γ initiates STAT1 pathway to induce priming of hippocampal microglia, thereby disrupts hippocampal microglia-neuron interactions and neural circuit link to social memory. Blocking STAT1 pathway or inhibiting microglial priming may be strategies to reduce the effects of IFN-γ on social behavior.

Microglial priming by IFN-γ involves STAT1-mediated activation of the NLRP3 inflammasome.

BACKGROUND: Inflammatory and immune responses in the brain that contribute to various neuropsychiatric disorders may begin as microglial "priming". Interferon (IFN)-γ is known to cause microglial priming, but the mechanism is unclear. METHODS: We examined the effects of IFN-γ on gene expression, microglial activation, inflammatory and immune responses and activity of the NLRP3 inflammasome in primary microglia and in the brains of mice. RESULTS: Our results showed that treating microglial cultures with IFN-γ induced a hedgehog-like morphology and upregulated markers of microglial activation (CD86, CD11b) and pro-inflammatory molecules (IL-1ß, IL-6, TNF-α, iNOS), while downregulating markers of microglial homeostasis (CX3CR1, CD200R1), anti-inflammatory molecules (MCR1, Arg-1) and neurotrophic factors (IGF-1, BDNF). IFN-γ also upregulated markers of NLRP3 inflammasome activation (NLRP3, caspase-1, gasdermin D, IL-18). This particular transcriptional profiling makes IFN-γ-primed microglia with exaggerated responses upon lipopolysaccharide (LPS) stimulation. The level of NLRP3, caspase-1, gasdermin D, IL-1ß, IL-18, TNF-α and iNOS in microglia cultures treated with both IFN-γ and LPS were highest than with either one alone. Injecting IFN-γ into the lateral ventricle of mice induced similar morphological and functional changes in hippocampal microglia as in primary microglial cultures. The effects of IFN-γ on NLRP3 inflammasome and microglia from cultures or hippocampus were abolished when STAT1 was inhibited using fludarabin. Injecting mice with IFN-γ alone or together with LPS induced anxiety- and depression-like behaviors and impaired hippocampus-dependent spatial memory; these effects were mitigated by fludarabin. CONCLUSIONS: IFN-γ primes microglia by activating STAT1, which upregulates genes that activate the NLRP3 inflammasome. Inhibiting the IFN-γ/STAT1 axis may be a way to treat neurodegenerative diseases and psychiatric disorders that involve microglial priming.

In situ nanoplasmonic probing of enzymatic activity of monolayer-confined glucose oxidase on colloidal nanoparticles.

In situ probing protein-particle interactions and activities of proteins on colloidal nanoparticle (NP) surfaces is a long-standing key challenge in understanding the nanobio interfaces and virtually important for a variety of biological and biomedical applications. The interactions of NPs with proteins, for instance, are known to form NP bioconjugates or protein coronas; protein surface immobilization and molecular layer-by-layer deposition techniques are widely used, but a clear understanding of the confinement effect on protein activity by molecular coating, at the monolayer level, remains poorly understood. We explore here a novel approach, using colloidal plasmonic nanocomplexes coated with glucose oxidase (GOx) as self-sensing nanoprobes for in situ optical probing of surface-confined enzymatic activity, which is at least 1-2 orders of magnitude more sensitive than standard colorimetric assays for detecting GOx activity. We found that enzymatic activity of monolayer-confined GOx on colloidal NPs was significantly enhanced as compared with free GOx (also proved by conformational changes from circular dichroism studies), with a low apparent Michaelis-Menten constant Km of ~0.115 mM and high turnover kcat/Km of ~8394 M(-1)·s(-1); compared with the "anchored-type" suspending GOx, the outmost polyelectrolyte monolayer-protected "sandwiched-type" GOx exhibits significantly improved enzymatic activities toward higher temperatures and wider pH range. This finding is of fundamental important and instructive for safe use of such nanomaterials for bioapplications.

Inorganic-organic competitive coating strategy derived uniform hollow gradient-structured ferroferric oxide-carbon nanospheres for ultra-fast and long-term lithium-ion battery.

The gradient-structure is ideal nanostructure for conversion-type anodes with drastic volume change. Here, we demonstrate an inorganic-organic competitive coating strategy for constructing gradient-structured ferroferric oxide-carbon nanospheres, in which the deposition of ferroferric oxide nanoparticles and polymerization of carbonaceous species are competitive and well controlled by the reaction thermodynamics. The synthesized gradient-structure with a uniform size of ~420 nm consists of the ferroferric oxide nanoparticles (4-8 nm) in carbon matrix, which are aggregated into the inner layer (~15 nm) with high-to-low component distribution from inside to out, and an amorphous carbon layer (~20 nm). As an anode material, the volume change of the gradient-structured ferroferric oxide-carbon nanospheres can be limited to ~22% with ~7% radial expansion, thus resulting in stable reversible specific capacities of ~750 mAh g-1 after ultra-long cycling of 10,000 cycles under ultra-fast rate of 10 A g-1. This unique inorganic-organic competitive coating strategy bring inspiration for nanostructure design of functional materials in energy storage.

Recent advances in the synthesis of hierarchically mesoporous TiO2 materials for energy and environmental applications.

Because of their low cost, natural abundance, environmental benignity, plentiful polymorphs, good chemical stability and excellent optical properties, TiO2 materials are of great importance in the areas of physics, chemistry and material science. Much effort has been devoted to the synthesis of TiO2 nanomaterials for various applications. Among them, mesoporous TiO2 materials, especially with hierarchically porous structures, show great potential owing to their extraordinarily high surface areas, large pore volumes, tunable pore structures and morphologies, and nanoscale effects. This review aims to provide an overview of the synthesis and applications of hierarchically mesoporous TiO2 materials. In the first section, the general synthetic strategies for hierarchically mesoporous TiO2 materials are reviewed. After that, we summarize the architectures of hierarchically mesoporous TiO2 materials, including nanofibers, nanosheets, microparticles, films, spheres, core-shell and multi-level structures. At the same time, the corresponding mechanisms and the key factors for the controllable synthesis are highlighted. Following this, the applications of hierarchically mesoporous TiO2 materials in terms of energy storage and environmental protection, including photocatalytic degradation of pollutants, photocatalytic fuel generation, photoelectrochemical water splitting, catalyst support, lithium-ion batteries and sodium-ion batteries, are discussed. Finally, we outline the challenges and future directions of research and development in this area.