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•A novel Fe-TiO2-x/TiO2 S-scheme homojunction was constructed.•The Fe-TiO2-x/TiO2 exhibits optimized CO/CH4 generation rates of 122/22 μmol g-1h−1.•The role of OV and Fe in improving ...catalytic performance has been discussed.•The photocatalytic mechanism was detailedly analyzed.
CO2-to-high value-added chemicals via a photocatalytic route is of interest but strangled by the low efficiency. Herein, a novel Fe-TiO2-x/TiO2 S-scheme homojunction was designed and constructed by using a facile surface modification approach whereby oxygen vacancy (OV) and Fe introducing on the TiO2 nanorod surface. The as-synthesized Fe-TiO2-x/TiO2 S-scheme homojunction exhibits positive properties on promoting photocatalytic CO2 reduction: i) the nanorod structure provides numerous active sites and a radical charge transfer path; ii) the doped Fe and OV not only synergistically enhance light utilization but also promote CO2 adsorption; iii) the Fe-TiO2-x/TiO2 S-scheme homojunction benefits photoexcited charge separation and retains stronger redox capacity. Thanks to those good characters, the Fe-TiO2-x/TiO2 homojunction exhibits superior CO2 reduction performances with optimized CO/CH4 generation rates of 122/22 μmol g-1h−1 which exceed those of pure TiO2 by more than 9.4/7.3 folds and most currently reported catalytic systems. This manuscript develops a facile and universal approach to synthesize well-defined homojunction and may inspire the construction of other more high-efficiency photocatalysts toward CO2 reduction and beyond.
Extinguishing the previously acquired fear is critical for the adaptation of an organism to the ever-changing environment, a process requiring the engagement of GABAA receptors (GABAARs). GABAARs ...consist of tens of structurally, pharmacologically, and functionally heterogeneous subtypes. However, the specific roles of these subtypes in fear extinction remain largely unexplored. Here, we observed that in the medial prefrontal cortex (mPFC), a core region for mood regulation, the extrasynaptically situated, d-subunit-containing GABAARs GABAA(d)Rs, had a permissive role in tuning fear extinction in male mice, an effect sharply contrasting to the established but suppressive role by the whole GABAAR family. First, the fear extinction in individual mice was positively correlated with the level of GABAA(d)R expression and function in their mPFC. Second, knockdown of GABAA(d)R in mPFC, specifically in its infralimbic (IL) subregion, sufficed to impair the fear extinction in mice. Third, GABAA(d)R-deficient mice also showed fear extinction deficits, and re-expressing GABAA(d)Rs in the IL of these mice rescued the impaired extinction. Further mechanistic studies demonstrated that the permissive effect of GABAA(d)R was associated with its role in enabling the extinction-evoked plastic regulation of neuronal excitability in IL projection neurons. By contrast, GABAA(d)R had little influence on the extinction-evoked plasticity of glutamatergic transmission in these cells. Altogether, our findings revealed an unconventional and permissive role of extrasynaptic GABAA receptors in fear extinction through a route relying on nonsynaptic plasticity.
Fine and dispersed Mg–Ti–oxide inclusions, which act as heterogeneous nucleation sites for intragranular ferrite, have been acknowledged as an effective method for grain refinement. In this paper, ...the nucleation and growth mechanisms of ferrite on Mg–Ti-oxides surface were investigated through first-principles calculations and solid-state pressure bonding experiments. The calculated results show that the formation of cation vacancies is the limiting step for Mn solute atom absorption by Mg–Ti-oxides. As determined by the lower covalency and ionicity of the Mg–O bond compared to the Ti–O bond in Mg–Ti-oxides, Mn atoms will be efficiently absorbed by occupying the Mg vacancies. The experimental results demonstrate that MgTiO3 with the maximum Mn-depleted zone (MDZ) width is the most effective for ferrite nucleation, which is consistent with the calculation results. As a representative, the Fe(110)/MgTiO3(001) interface with the lowest planar disregistry (3.16%) was selected to analyze growth behaviors. Due to charge accumulation and variation, Fe atoms are more likely to gather on the Mg–O terminal MgTiO3(001) surface and form (Mg–O)–Fe-1 interfaces. Its adhesion work and interface energy are 1.74 and 2.46 J/m2, respectively. The present study illustrates the nucleation and growth mechanisms of ferrite on Mg–Ti-oxides, providing theoretical support for the application of Mg–Ti-oxide inclusions in oxide metallurgy.
Metformin, a first-line drug for type 2 diabetes mellitus (T2DM), has been found to reduce depressive symptoms in patients with comorbid depression and other diseases. However, it is largely unclear ...how metformin ameliorates depressive-like behaviors. Here, we used lipopolysaccharide (LPS) to induce depressive-like behaviors in mice and found that LPS-treated mice exhibited increased immobility in the forced swimming test (FST) and tail suspension test (TST), as well as increased glutamatergic transmission. Furthermore, metformin administration in the LPS-treated mice ameliorated depressive-like behaviors and elevated glutamatergic transmission. Our results suggest that metformin has antidepressant effects and can correct abnormal glutamatergic transmission, providing an insight into the underlying mechanism by which metformin acts against depression.
Metformin (Met) is a first-line drug for type 2 diabetes mellitus (T2DM). Numerous studies have shown that Met exerts beneficial effects on a variety of neurological disorders, including Alzheimer’s ...disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). However, it is still largely unclear how Met acts on neurons. Here, by treating acute hippocampal slices with Met (1 μM and 10 μM) and recording synaptic transmission as well as neuronal excitability of CA1 pyramidal neurons, we found that Met treatments significantly increased the frequency of miniature excitatory postsynaptic currents (mEPSCs), but not amplitude. Neither frequency nor amplitude of miniature inhibitory postsynaptic currents (mIPSCs) were changed with Met treatments. Analysis of paired-pulse ratios (PPR) demonstrates that enhanced presynaptic glutamate release from terminals innervating CA1 hippocampal pyramidal neurons, while excitability of CA1 pyramidal neurons was not altered. Our results suggest that Met preferentially increases glutamatergic rather than GABAergic transmission in hippocampal CA1, providing a new insight on how Met acts on neurons.
Neuregulin3 (NRG3) is a growth factor of the neuregulin (NRG) family and a risk gene of various severe mental illnesses including schizophrenia, bipolar disorders, and major depression. However, the ...physiological function of NRG3 remains poorly understood. Here we show that loss of Nrg3 in GFAP-Nrg3f/f
mice increased glutamatergic transmission, but had no effect on GABAergic transmission. These phenotypes were observed in Nex-Nrg3f/f
mice, where Nrg3 was specifically knocked out in pyramidal neurons, indicating that Nrg3 regulates glutamatergic transmission by a cell-autonomous mechanism. Consequently, in the absence of Nrg3 in pyramidal neurons, mutant mice displayed various behavioral deficits related to mental illnesses. We show that the Nrg3 mutation decreased paired-pulse facilitation, increased decay of NMDAR currents when treated with MK801, and increased minimal stimulation-elicited response, providing evidence that the Nrg3 mutation increases glutamate release probability. Notably, Nrg3 is a presynaptic protein that regulates the SNARE-complex assembly. Finally, increased Nrg3 levels, as observed in patients with severe mental illnesses, suppressed glutamatergic transmission. Together, these observations indicate that, unlike the prototype Nrg1, the effect of which is mediated by activating ErbB4 in interneurons, Nrg3 is critical in controlling glutamatergic transmission by regulating the SNARE complex at the presynaptic terminals, identifying a function of Nrg3 and revealing a pathophysiological mechanism for hypofunction of the glutamatergic pathway in Nrg3-related severe mental illnesses.
Dendritic cell nuclear protein-1 (DCNP1) is a protein associated with major depression. In the brains of depression patients, DCNP1 is up-regulated. However, how DCNP1 participates in the ...pathogenesis of major depression remains unknown. In this study, we first transfected HEK293 cells with EGFP-DCNP1 and demonstrated that the full-length DCNP1 protein was localized in the nucleus, and RRK (the residues 117-119) composed its nuclear localization signal (NLS). An RRK-deletion form of DCNP1 (DCNP1
) and truncated form (DCNP1
), each lacking the RRK residues, did not show the specific nuclear localization like full-length DCNP1 in the cells. A rat glioma cell line C6 can synthesize melatonin, a hormone that plays important roles in both sleep and depression. We then revealed that transfection of C6 cells with full-length DCNP1 but not DCNP1
or DCNP1
significantly decreased the levels of melatonin. Furthermore, overexpression of full-length DCNP1, but not DCNP1
or DCNP1
, in C6 cells significantly decreased both the mRNA and protein levels of N-acetyltransferase (NAT), a key enzyme in melatonin synthesis. Full-length DCNP1 but not DCNP1
or DCNP1
was detected to interact with the Nat promoter and inhibited its activity through its E-box motif. Furthermore, full-length DCNP1 but not the mutants interacted with and repressed the transcriptional activity of BMAL1, a transcription factor that transactivates Nat through the E-box motif. In conclusion, we have shown that RRK (the residues 117-119) are the NLS responsible for DCNP1 nuclear localization. Nuclear DCNP1 represses NAT expression and melatonin biosynthesis by interacting with BMAL1 and repressing its transcriptional activity. Our study reveals a connection between the major depression candidate protein DCNP1, circadian system and melatonin biosynthesis, which may contribute to the pathogenesis of depression.
Extinguishing the previously acquired fear is critical for the adaptation of an organism to the ever-changing environment, a process requiring the engagement of GABA
receptors (GABA
Rs). GABA
Rs ...consist of tens of structurally, pharmacologically, and functionally heterogeneous subtypes. However, the specific roles of these subtypes in fear extinction remain largely unexplored. Here, we observed that in the medial prefrontal cortex (mPFC), a core region for mood regulation, the extrasynaptically situated, δ-subunit-containing GABA
Rs GABA
(δ)Rs, had a permissive role in tuning fear extinction in male mice, an effect sharply contrasting to the established but suppressive role by the whole GABA
R family. First, the fear extinction in individual mice was positively correlated with the level of GABA
(δ)R expression and function in their mPFC. Second, knockdown of GABA
(δ)R in mPFC, specifically in its infralimbic (IL) subregion, sufficed to impair the fear extinction in mice. Third, GABA
(δ)R-deficient mice also showed fear extinction deficits, and re-expressing GABA
(δ)Rs in the IL of these mice rescued the impaired extinction. Further mechanistic studies demonstrated that the permissive effect of GABA
(δ)R was associated with its role in enabling the extinction-evoked plastic regulation of neuronal excitability in IL projection neurons. By contrast, GABA
(δ)R had little influence on the extinction-evoked plasticity of glutamatergic transmission in these cells. Altogether, our findings revealed an unconventional and permissive role of extrasynaptic GABA
receptors in fear extinction through a route relying on nonsynaptic plasticity.
The medial prefrontal cortex (mPFC) is one of the kernel brain regions engaged in fear extinction. Previous studies have repetitively shown that the GABA
receptor (GABA
R) family in this region act to suppress fear extinction. However, the roles of specific GABA
R subtypes in mPFC are largely unknown. We observed that the GABA
R-containing δ-subunit GABA
(δ)R, a subtype of GABA
Rs exclusively situated in the extrasynaptic membrane and mediating the tonic neuronal inhibition, works oppositely to the whole GABA
R family and promotes (but does not suppress) fear extinction. More interestingly, in striking contrast to the synaptic GABA
Rs that suppress fear extinction by breaking the extinction-evoked plasticity of glutamatergic transmission, the GABA
(δ)R promotes fear extinction through enabling the plastic regulation of neuronal excitability in the infralimbic subregion of mPFC. Our findings thus reveal an unconventional role of GABA
(δ)R in promoting fear extinction through a route relying on nonsynaptic plasticity.
This work reports a simple enzyme-linked hybrid-sandwich assay (ELHSA) for one vital cardiac biomarker, cardiac troponin I (cTnI). Aimed at expanding the "antibody-antigen" immunoassay, a distinct ..."capture antibody-target-detection aptamer" configuration was designed, in which two types of recognition elements were involved. Through systematical study, optimal antibody-aptamer combination and amount ratio between streptavidin-horseradish peroxidase conjugate and biotin-modified aptamer were obtained, and a beneficial interaction mode between cTnI and the two recognition elements was disclosed, namely, cTnI protein binding to the aptamer could be well recognized by antibody, but not vice versa. Moreover, it was first found that, apart from as a blocking agent, bovine serum albumin could be introduced in the detection probe solution as an enhancer, leading to high sensitivity and reproducibility. The BSA-assisted ELHSA can detect as low as 0.24 ng/mL cTnI and is a new, simple and effective strategy to apparently improve ELHSA for cTnI detection. Meanwhile, prominent selectivity derived from dual specific recognition elements and good applicability indicate that the developed ELHSA for cTnI is anticipated to substitute classical ELISA for diagnosis of cardiovascular diseases in the future.
Background
Brain arteriovenous malformation (bAVM)-related epilepsy can significantly affect patient quality of life. We aimed to identify the factors associated with seizures occurrence and evaluate ...the long-term outcome following Onyx embolization in bAVM patients.
Methods
Between July 2014 and July 2016, 239 consecutive patients underwent treatment for bAVMs in our institute and were respectively analyzed. Demographics, seizure status and bAVM morphologic characteristics were recorded. Modified Engel classification was used to evaluate the long-term seizure outcomes.
Results
Of 239 bAVM patients, 68 (28.5%) initially presented with seizures. Seizure occurrence was associated with cerebral hemorrhage history, frontal-temporal location and arterial borderzone location. Of the 37 patients who presented with initial seizures and were treated with Onyx embolization, 23 (62.2%) were treated with antiepileptic drugs (AEDs) before Onyx embolization. At the last follow-up visit, 19 (51.4%) of the 37 patients reached modified Engel class I outcome. Of the 23 patients who had ever been treated with AEDs, 12 (52.2%) were still taking AEDs at the last follow-up visit. Single-factor analysis showed that arterial borderzone location was significantly correlated with higher modified Engel class outcome (p = 0.046).
Conclusion
Patients with bAVM hemorrhage history, frontal-temporal location and arterial borderzone location were associated with seizure occurrence. Seizure-free status was not obtained in AVM patients with arterial borderzone after embolization, though it may have benefits in other ways. The seizure-free mechanism of bAVM with Onyx embolization is worth further study.
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