TGR5-mediated lateral hypothalamus-dCA3-dorsolateral septum circuit regulates depressive-like behavior in male mice.

Although bile acids play a notable role in depression, the pathological significance of the bile acid TGR5 membrane-type receptor in this disorder remains elusive. Using depression models of chronic social defeat stress and chronic restraint stress in male mice, we found that TGR5 in the lateral hypothalamic area (LHA) predominantly decreased in GABAergic neurons, the excitability of which increased in depressive-like mice. Upregulation of TGR5 or inhibition of GABAergic excitability in LHA markedly alleviated depressive-like behavior, whereas down-regulation of TGR5 or enhancement of GABAergic excitability facilitated stress-induced depressive-like behavior. TGR5 also bidirectionally regulated excitability of LHA GABAergic neurons via extracellular regulated protein kinases-dependent Kv4.2 channels. Notably, LHA GABAergic neurons specifically innervated dorsal CA3 (dCA3) CaMKIIα neurons for mediation of depressive-like behavior. LHA GABAergic TGR5 exerted antidepressant-like effects by disinhibiting dCA3 CaMKIIα neurons projecting to the dorsolateral septum (DLS). These findings advance our understanding of TGR5 and the LHAGABA→dCA3CaMKIIα→DLSGABA circuit for the development of potential therapeutic strategies in depression.

Neuroprotective effects of novel compound FMDB on cognition, neurogenesis and apoptosis in APP/PS1 transgenic mouse model of Alzheimer's disease.

Clinical and experimental studies have shown that the sharp reduction of estrogen is one of the important reasons for the high incidence of Alzheimer's disease (AD) in elderly women, but there is currently no such drug for treatment of AD. Our group first designed and synthesized a novel compound R-9-(4fluorophenyl)-3-methyl-10,10,-Hydrogen-6-hydrogen-benzopyran named FMDB. In this study, our aim is to investigate the neuroprotective effects and mechanism of FMDB in APP/PS1 transgenic mice. 6 months old APP/PS1 transgenic mice were intragastrical administered with FMDB (1.25, 2.5 and 5 mg/kg) every other day for 8 weeks. LV-ERß-shRNA was injected bilaterally into the hippocampus of APP/PS1 mice to knockdown estrogen receptor ß (ERß). We found that FMDB ameliorated cognitive impairment in the Morris water maze and novel object recognition tests, increased hippocampal neurogenesis and prevented hippocampal apoptotic responses in APP/PS1 mice. Importantly, FMDB activated nuclear ERß mediated CBP/p300, CREB and brain-derived neurotrophic factor (BDNF) signaling, and membrane ERß mediated PI3K/Akt, CREB and BDNF signaling in the hippocampus. Our study demonstrated the contributions and mechanism of FMDB to cognition, neurogenesis and apoptosis in APP/PS1 mice. These lay the experimental foundation for the development of new anti-AD drugs.

Deficiency of astrocyte CysLT1R ameliorates depression-like behaviors in mice by modulating glutamate synaptic transmission.

Our previous study suggests that hippocampal cysteinyl leukotriene receptor 1 (CysLT1R) could be involved in depression. Herein we hypothesize that CysLT1R may regulate depression by affecting synaptic glutamate cycling based on existence of CysLT1R in the astrocytes that participate in occurrence of depression. We found that CysLT1R expression was significantly increased in the astrocyte of chronic unpredictable mild stress (CUMS)-induced depression-like mice, CysLT1R astrocyte-specific conditional knockout (AcKO) significantly improved depression-like behaviors, as indicated by decreased immobility time in the forced swimming test and tail suspension test and increased sucrose preference in the sucrose preference test, and knockdown of CysLT1R in the astrocyte of dentate gyrus (DG), the region with the most significant increase of CysLT1R in the astrocyte of depression-like mice, produced similar effects. Correspondingly, overexpression of CysLT1R in the astrocyte of DG induced depression-like behaviors in mice. The further study showed that CysLT1R AcKO ameliorated synaptic plasticity impairment, as reflected by increased synapse, LTP and PSD95, and promoted glutamate transporter 1 (GLT-1) expression by inhibiting NF-κB p65 nuclear translocation mediated by ß-arestin2 and clatrhin, subsequently decreased glutamate in synaptic cleft and GluN2B on postsynaptic membrane in depression-like mice. The present study also showed that GLT-1 agonist or NF-κB inhibitor ameliorated depressive-like behaviors induced by overexpression of the astrocyte CysLT1R of DG. Our study demonstrated that astrocyte CysLT1R regulated depression by modulating glutamate synaptic transmission, suggesting that CysLT1R could be a potential target for developing novel drugs of anti-depression.

A cholinergic medial septum input to medial habenula mediates generalization formation and extinction of visual aversion.

Generalization of visual aversion is a critical function of the brain that supports survival, but the underlying neurobiological mechanisms are unclear. We establish a rapid generalization procedure for inducing visual aversion by dynamic stripe images. By using fiber photometry, apoptosis, chemogenetic and optogenetic techniques, and behavioral tests, we find that decreased cholinergic neurons' activity in the medial septum (MS) leads to generalization loss of visual aversion. Strikingly, we identify a projection from MS cholinergic neurons to the medial habenula (MHb) and find that inhibition of the MS→MHb cholinergic circuit disrupts aversion-generalization formation while its continuous activation disrupts subsequent extinction. Further studies show that MS→MHb cholinergic projections modulate the generalization of visual aversion possibly via M1 muscarinic acetylcholine receptors (mAChRs) of downstream neurons coreleasing glutamate and acetylcholine. These findings reveal that the MS→MHb cholinergic circuit is a critical node in aversion-generalization formation and extinction and potentially provides insight into the pathogenesis of affective disorders.

Activation of TGR5 Ameliorates Streptozotocin-Induced Cognitive Impairment by Modulating Apoptosis, Neurogenesis, and Neuronal Firing.

Takeda G protein-coupled receptor 5 (TGR5) is the first known G protein-coupled receptor specific for bile acids and is recognized as a new and critical target for type 2 diabetes and metabolic syndrome. It is expressed in many brain regions associated with memory such as the hippocampus and frontal cortex. Here, we hypothesize that activation of TGR5 may ameliorate streptozotocin- (STZ-) induced cognitive impairment. The mouse model of cognitive impairment was established by a single intracerebroventricular (ICV) injection of STZ (3.0 mg/kg), and we found that TGR5 activation by its agonist INT-777 (1.5 or 3.0 µg/mouse, ICV injection) ameliorated spatial memory impairment in the Morris water maze and Y-maze tests. Importantly, INT-777 reversed STZ-induced downregulation of TGR5 and glucose usage deficits. Our results further showed that INT-777 suppressed neuronal apoptosis and improved neurogenesis which were involved in tau phosphorylation and CREB-BDNF signaling. Moreover, INT-777 increased action potential firing of excitatory pyramidal neurons in the hippocampal CA3 and medial prefrontal cortex of ICV-STZ groups. Taken together, these findings reveal that activation of TGR5 has a neuroprotective effect against STZ-induced cognitive impairment by modulating apoptosis, neurogenesis, and neuronal firing in the brain and TGR5 might be a novel and potential target for Alzheimer's disease.

Directly decorated CeY zeolite for O2-selective adsorption in O2/N2 separation at ambient temperature.

The traditional zeolites used in air separation are generally N2-selective adsorbents. It was found for the first time that the O2/N2 adsorption selectivity can be reversed by directly decorating the Ce metal ion sites of a traditional Y zeolite with imidazole molecules, which results in a novel O2 adsorbent. The O2/N2 selectivity changes from 0.9 to 1.6 under normal conditions, and most importantly, the O2 adsorbent is recyclable. The in situ XPS characterization results indicate that the imidazole modification can change the electronic state of Ce in the Y zeolite and increase its affinity for O2, which is confirmed by theoretical calculations. Dynamic breakthrough adsorption experiments show that the adsorbent has significant application potential in air separation.

Hippocampal CysLT1R overexpression or activation accelerates memory deficits, synaptic dysfunction, and amyloidogenesis in young APP/PS1 transgenic mice.

BACKGROUND: Our previous studies demonstrated that cysteinyl leukotrienes receptor 1 (CysLT1R) knockout, pharmacological blockade, or hippocampus knockdown produced beneficial effects against Alzheimer's disease (AD); however, whether CysLT1R upregulation has deleterious effects on AD remains elusive. METHODS: In this study, we investigated the changes in behaviors, hippocampal amyloidogenesis, and synapse plasticity after CysLT1R overexpression by microinfusion of the lentiviral vector, containing its coding sequence of mouse (LV-CysLT1R), into the bilateral dentate gyri (DG) of the hippocampus or CysLT1R activation by repeated systemic administration of its agonist YM-17690 (0.1 mg/kg, once a day, i.p., for 28 d). RESULTS: The behavior data showed that overexpression of CysLT1R in hippocampal DG or administration of YM-17690 deteriorated behavioral performance in Morris water maze (MWM), Y-maze tests, and novel object recognition (NOR) in young APP/PS1 mice. The further studies showed that these treatments significantly destroyed synaptic function, as evidenced by impaired hippocampal long-term potentiation (LTP), decreased spine density, low number of synapses, and decreased postsynaptic protein (PSD95), and promoted the generation of amyloid ß (Aß) through increased expression of BACE1 and PS1 in the hippocampus of young APP/PS1 mice. CONCLUSIONS: Together, our results indicate that CysLT1R upregulation accelerates memory impairment in young APP/PS1 mice, which is associated with promoting synaptic dysfunction and amyloidogenesis in the hippocampus.

Efficient Separation of Xylene Isomers by a Pillar-Layer Metal-Organic Framework.

The separation of xylene isomers is one of the most challenging issues in the chemical industry because of the similarity of their boiling points and kinetic diameters. This study focuses on the use of pillar-layer MOF-Co(aip)(bpy)0.5 for adsorption and separation of xylene isomers. It was found that Co(aip)(bpy)0.5 exhibited a significant para-selectivity in liquid-phase competitive adsorption of xylene isomers, and the competitive separation factors reached as high as 30 for p-xylene versus m-xylene and 16 for p-xylene versus o-xylene. Desorption experiments further confirmed the preferential adsorption of p-xylene on the adsorbent. Molecular simulations and calculations revealed that the order of interaction strengths for xylene molecules and the adsorbent framework was p-xylene ≫ o-xylene ≈ m-xylene, which illustrated the selective adsorption phenomena arising from the mechanism for microscopic interactions. This work broadens the application of pillar-layer MOF materials in the field of xylene isomer adsorption and separation.

Takeda G Protein-Coupled Receptor 5 Modulates Depression-like Behaviors via Hippocampal CA3 Pyramidal Neurons Afferent to Dorsolateral Septum.

BACKGROUND: Takeda G protein-coupled receptor 5 (TGR5) is recognized as a promising target for type 2 diabetes and metabolic syndrome; its expression has been demonstrated in the brain and is thought to be neuroprotective. Here, we hypothesize that dysfunction of central TGR5 may contribute to the pathogenesis of depression. METHODS: In well-established chronic social defeat stress (CSDS) and chronic restraint stress (CRS) models of depression, we investigated the functional roles of TGR5 in CA3 pyramidal neurons (PyNs) and underlying mechanisms of the neuronal circuit in depression (for in vivo studies, n = 10; for in vitro studies, n = 5-10) using fiber photometry; optogenetic, chemogenetic, pharmacological, and molecular profiling techniques; and behavioral tests. RESULTS: Both CSDS and CRS most significantly reduced TGR5 expression of hippocampal CA3 PyNs. Genetic overexpression of TGR5 in CA3 PyNs or intra-CA3 infusion of INT-777, a specific agonist, protected against CSDS and CRS, exerting significant antidepressant-like effects that were mediated via CA3 PyN activation. Conversely, genetic knockout or TGR5 knockdown in CA3 facilitated stress-induced depression-like behaviors. Re-expression of TGR5 in CA3 PyNs rather than infusion of INT-777 significantly improved depression-like behaviors in Tgr5 knockout mice exposed to CSDS or CRS. Silencing and stimulation of CA3 PyNs→somatostatin-GABAergic (gamma-aminobutyric acidergic) neurons of the dorsolateral septum circuit bidirectionally regulated depression-like behaviors, and blockade of this circuit abrogated the antidepressant-like effects from TGR5 activation of CA3 PyNs. CONCLUSIONS: These findings indicate that TGR5 can regulate depression via CA3 PyNs→somatostatin-GABAergic neurons of dorsolateral septum transmission, suggesting that TGR5 could be a novel target for developing antidepressants.

Separation of Xylene Isomers in the Anion-Pillared Square Grid Material SIFSIX-1-Cu.

Xylene isomer separation is considered one of the seven separation challenges that changed the world. In addition, the high-energy demand of xylene separation highlights the need for efficient novel adsorbents. Herein, the liquid-phase separation potential of the anion-pillared hybrid material SIFSIX-1-Cu was studied for preferential adsorption of o-xylene and m-xylene over p-xylene, which was inspired by a previous complexation crystallization method for separating m-xylene. We report detailed experimental liquid-phase adsorption experiments, yielding selectivities of 3.0 for o-xylene versus p-xylene and 2.6 for m-xylene versus p-xylene. Our theoretical calculations thus provide a reasonable explanation that the xylene adsorption selectivity is attributed to the C-H⋅⋅⋅F interaction, and the host-guest interaction order agrees with the adsorption priority: o-xylene > m-xylene > p-xylene.

Preparation of Efficient Ultraviolet-Protective Transparent Coating by Using a Titanium-Containing Hybrid Oligomer.

Ultraviolet (UV) radiation is closely related to people's lives, but excess UV exposure has led to a series of problems. UV protection technology plays a vital role in our life. The most commonly adopted UV protection technology is to use UV-absorbing materials to make protective coatings, including sunscreen cream for human skin and sunscreen coating for materials. Conventional organic UV-protective coatings have low stability and are sensitive to heat, while inorganic UV-protective coating with highly efficient UV-protective performance usually need high processing temperatures and exhibit low transparency. Here, we report a Ti-PEG-Si cross-linked inorganic-organic hybrid material, which exhibits good UV-absorbing performance. By using these UV-absorbing materials, an efficient transparent UV-absorbing coating could be easily prepared at room temperature (298 K). The UV-absorbing coating is mainly composed of titanium and silicon connected by PEG200. PEG200 as a cross-linker can improve the UV-absorption performance of the coating and increase its visible light transmittance. At the same time, the existence of PEG200 can effectively increase the stability and elasticity of the coating and maintain its mechanical properties after UV irradiation. Furthermore, the coating could maintain highly UV-protective performance and could be transparent even after thermal treatment at high temperature (973 K). From this point of view, the hybrid materials have considerable application potential in next-generation UV protective coatings, especially with their utilization in heat-sensitive substrates or under high-temperature conditions.

Oxygen-selective adsorption on high-silica LTA zeolite.

The adsorption capacity of O2 and N2 on a LTA-type zeolite can be significantly affected by the change of its Si/Al ratio. With the increase in Si/Al ratio and the decrease in the amount of Na+, the protonated high-silica LTA zeolite changes from being a N2-selective sorbent to an O2-selective sorbent to reverse the O2 and N2 selectivity.

Enhanced Propene/Propane Separation by Directional Decoration of the 12-Membered Rings of Mordenite with ZIF Fragments.

Propene/propane separation is challenging due to the very small difference in molecular sizes, boiling points and condensabilities between these molecules. Herein, we report a strategy of introducing ZIF fragments into traditional mordenite (MOR) zeolite to decorate the 12-membered ring of MOR. After decoration, the originally ineffective zeolite MOR exhibited high kinetic propene/propane selectivities (139 at 25 °C) and achieved efficient propene/propane separation. The propene/propane separation potentials of the resulting adsorbents were further confirmed by breakthrough experiments with equimolar propene/propane (50/50) mixtures.

Decorated Traditional Zeolites with Subunits of Metal-Organic Frameworks for CH4 /N2 Separation.

Metal-organic frameworks (MOF) materials are promising materials for gas separation, but their application still faces various challenges. A strategy is now reported for introducing subunits of MOFs into traditional zeolite frameworks to obtain applicable adsorbents with advantages of both zeolites and MOFs. The subunits of ZIFs were introduced into zeolite Y and zeolite ZSM-5 for CH4 /N2 separation. Both the molecular simulation and experimental results validated that the IAST CH4 /N2 selectivity of the resulting samples greatly improved (above 8, at 100 kPa and 25 °C) with the incorporation of ZIF subunits into zeolites structure, and the selectivities were obviously higher than that of zeolites and even better than that of ZIFs. This strategy not only gave rise to an efficient adsorbent for CH4 /N2 separation but also provided ideas for design of other adsorption and separation materials.

Hydrothermal synthesis of high silica zeolite Y using tetraethylammonium hydroxide as a structure-directing agent.

High silica zeolite Y with a SiO2/Al2O3 ratio of 7.76 is successfully synthesized with tetraethylammonium hydroxide (TEAOH) as a structure-directing agent. The high silica zeolite Y shows outstanding high temperature thermal stability and hydrothermal stability.

Attenuation of Oxidative Stress of Erythrocytes by Plant-Derived Flavonoids, Orientin and Luteolin.

Erythrocytes are easy to be injured by oxidative stress in their lifespan. Although there are several chemicals such as vitamin C (VC) that would be able to reduce oxidative stress, natural herbal products still remain an interesting research area. The current study investigated the effects of two plant-derived flavonoids, orientin and luteolin, on erythrocytes and their possible mechanisms. This experiment was divided into nine groups, which were normal group, model group, VC control group, and treated groups with different doses of orientin and luteolin (10, 20, and 40 µg/mL), respectively. Hemolysis rate was determined by spectrophotometry. Antioxidative enzyme and products were evaluated by different methods. Erythrocyte cell surface and cellular structure were observed with scanning or transmission electron microscope, respectively. Oxidative stress induced significant increase in hemolysis rate of erythrocytes. Orientin or luteolin ameliorated hemolysis of erythrocytes in oxidative stress in a dose-dependent manner. Both orientin and luteolin reduced oxidative products and increased antioxidative enzyme activities. Moreover, orientin and luteolin attenuated oxidative stress induced damage of erythrocyte cell surface morphology and cellular structure. In conclusion, orientin and luteolin could protect human erythrocytes from oxidative damage by attenuating oxidative stress, protecting antioxidative enzyme activities, and preserving integrity of erythrocyte structure.

Mixed hemimicelles solid-phase extraction based on ionic liquid-coated Fe3O4/SiO2 nanoparticles for the determination of flavonoids in bio-matrix samples coupled with high performance liquid chromatography.

A novel magnetic solid-phase extraction (MSPE) method based on mixed hemimicelles of room temperature ionic liquids (RTILs) coated Fe3O4/SiO2 nanoparticles (NPs) was developed for simultaneous extraction of trace amounts of flavonoids in bio-matrix samples. A comparative study on the use of RTILs (C16mimBr) and CTAB-coated Fe3O4/SiO2 NPs as sorbents was presented. Owing to bigger adsorption amounts for analytes, RTILs-coated Fe3O4/SiO2 NPs was selected as MSPE materials and three analytes luteolin, quercetin and kaempferol can be quantitatively extracted and simultaneously determined coupled with high performance liquid chromatography (HPLC) in urine samples. No interferences were caused by proteins or endogenous compounds. Good linearity (R(2)>0.9993) for all calibration curves was obtained, and the limits of detection (LOD) for luteolin, quercetin and kaempferol were 0.10 ng/mL, 0.50 ng/mL and 0.20 ng/mL in urine samples, respectively. Satisfactory recoveries (93.5-97.6%, 90.1-95.4% and 93.3-96.6% for luteolin, quercetin and kaempferol) in biological matrices were achieved. It was notable that while using a small amount of Fe3O4/SiO2 NPs (4.0 mg) and C16mimBr (1.0 mg), satisfactory preconcentration factors and extraction recoveries for the three flavonoids were obtained. To the best of our knowledge, this is the first time a mixed hemimicelles MSPE method based on RTILs and Fe3O4/SiO2 NPs magnetic separation has ever been used for pretreatment of complex biological samples.

Preparation of molecularly imprinted polymers on the surface of magnetic carbon nanotubes with a pseudo template for rapid simultaneous extraction of four fluoroquinolones in egg samples.

Fluoroquinolones (FQs) have emerged as one of the most important class of antibiotics. Due to their low concentration in bio-matrix samples which contain a lot of interfering substances, the efficient solid phase extraction and accurate determination of FQs remain a challenge. In this paper, a new strategy for the isolation and enrichment of FQs from egg samples was obtained by molecularly imprinted polymers on the surface of magnetic carbon nanotubes (MCNTs@MIP), which not only can be collected and separated rapidly by an external magnetic field, but also have a high specific surface area, outstanding mechanical properties and specific recognition for FQs. MCNTs@MIP were prepared using ofloxacin as a pseudo template, methacrylic acid as a functional monomer, and ethylene glycol dimethacrylate as a cross-linker. The characteristics of the MCNTs@MIP were assessed by transmission electron microscopy (TEM), multipoint Brunauer-Emmett-Teller (BET) analysis, vibrating sample magnetometry (VSM), X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectroscopy. The results of the adsorption experiments not only demonstrated rapid dynamic adsorption but also showed a high selectivity toward FQs. An extraction method using MCNTs@MIP coupled with high performance liquid chromatography (HPLC) was developed for the determination of four FQs in egg samples. The recovery of four FQs ranged from 95.2% ± 3.2% to 100.7% ± 3.1% and the detection limits ranged from 0.25-0.40 ng g(-1). The results demonstrate that the proposed method based on pseudo template MCNTs@MIP is a promising approach for the preconcentration, purification, and simultaneous analysis of four FQs in bio-matrix samples.

Microwave-assisted one-step green synthesis of amino-functionalized fluorescent carbon nitride dots from chitosan.

We present an economical, facile and effective microwave pyrolysis approach to synthesize highly amino-functionalized fluorescent carbon nitride dots (CNDs). The formation and the functionalization of CNDs was accomplished simultaneously through the dehydration of chitosan. It is suggested that these CNDs have good water solublility and exhibit strong fluorescence.

Development of novel molecularly imprinted magnetic solid-phase extraction materials based on magnetic carbon nanotubes and their application for the determination of gatifloxacin in serum samples coupled with high performance liquid chromatography.

A novel composite imprinted material, on the basis of magnetic carbon nanotubes (MCNTs)-incorporated layer using gatifloxacin as a template, methacrylic acid as a functional monomer, and ethylene glycol dimethacrylate as a cross-linker, was successfully synthesized by a surface imprinting technique. Adsorption dynamics and a Scatchard adsorption model were employed to evaluate the adsorption process. The results showed that magnetic carbon nanotubes molecularly imprinted polymers (MCNTs@MIP) displayed a rapid dynamic adsorption and a high adsorption capacity of 192.7 µg/mg toward GTFX. Applied MCNTs@MIP as a sorbent, a magnetic solid phase extraction method coupled with high performance liquid chromatography (MSPE-HPLC) was developed for the determination of GTFX in serum samples. The recoveries from 79.1±4.8% to 85.3±4.2% were obtained. MCNTs@MIP can not only be collected and separated fast by external magnetic field but also have high surface-to-volume ratio, outstanding mechanical properties and specific recognition toward template molecule. In addition, the MCNTs@MIP could be regenerated, which could be used for five cycles with lost of less than 7.8% of its recovery on average. These analytical results of serum samples display that the proposed method based on MCNTs@MIP is applicable for fast and selective extraction of therapeutic agents from biological fluids.