The GABAergic pathway from anterior cingulate cortex to lateral hypothalamus area regulates irritable bowel syndrome in mice and its underlying mechanism.

Irritable bowel syndrome (IBS), which is characterized by chronic abdominal pain, has a high global prevalence. The anterior cingulate cortex (ACC), which is a pivotal region involved in pain processing, should be further investigated regarding its role in the regulation of visceral sensitivity and mental disorders. A C57BL/6J mouse model for IBS was established using chronic acute combining stress (CACS). IBS-like symptoms were assessed using behavioral tests, intestinal motility measurements, and abdominal withdrawal reflex scores. Fluoro-Gold retrograde tracing and immunohistochemistry techniques were employed to investigate the projection of ACC gamma-aminobutyric acid-producing (GABAergic) neurons to the lateral hypothalamus area (LHA). Chemogenetic approaches enabled the selective activation or inhibition of the ACC-LHA GABAergic pathway. Enzyme-linked immunosorbent assay (ELISA) and western blot analyses were conducted to determine the expression of histamine, 5-hydroxytryptamine (5-HT), and transient receptor potential vanilloid 4 (TRPV4). Our findings suggest that CACS induced IBS-like symptoms in mice. The GABA type A receptors (GABAAR) within LHA played a regulatory role in modulating IBS-like symptoms. The chemogenetic activation of ACC-LHA GABAergic neurons elicited anxiety-like behaviors, intestinal dysfunction, and visceral hypersensitivity in normal mice; however, these effects were effectively reversed by the administration of the GABAAR antagonist Bicuculline. Conversely, the chemogenetic inhibition of ACC-LHA GABAergic neurons alleviated anxiety-like behaviors, intestinal dysfunction, and visceral hypersensitivity in the mouse model for IBS. These results highlight the crucial involvement of the ACC-LHA GABAergic pathway in modulating anxiety-like behaviors, intestinal motility alterations, and visceral hypersensitivity, suggesting a potential therapeutic strategy for alleviating IBS-like symptoms.

The role of ncRNAs in depression.

Depressive disorders have a significant impact on public health, and depression have an unsatisfactory recurrence rate and are challenging to treat. Non-coding RNAs (ncRNAs) are RNAs that do not code protein, which have been shown to be crucial for transcriptional regulation. NcRNAs are important to the onset, progress and treatment of depression because they regulate various physiological functions. This makes them distinctively useful as biomarkers for diagnosing and tracking responses to therapy among individuals with depression. It is important to seek out and summarize the research findings on the impact of ncRNAs on depression since significant advancements have been made in this area recently. Hence, we methodically outlined the findings of published researches on ncRNAs and depression, focusing on microRNAs. Above all, this review aims to improve our understanding of ncRNAs and provide new insights of the diagnosis and treatment of depression.

Regulation of the MCHergic Neural Circuit to Dorsal Raphe Nucleus on Emotion-Related Behaviors and Intestinal Dysfunction in Mice Model of Irritable Bowel Syndrome with Diarrhea.

INTRODUCTION: Irritable bowel syndrome with diarrhea (IBS-D) is frequently accompanied by depression and anxiety, resulting in a reduced quality of life and increased medical expenditures. Although psychological factors are known to play an important role in the genesis and development of IBS-D, an understanding of the central neural control of intestinal dysfunction remains elusive. Melanin-concentrating hormone (MCH) is a gut-brain peptide involved in regulating feeding, sleep-wake rhythms, and emotional states. METHODS: This study investigated the regulation of the MCHergic neural circuit from the lateral hypothalamic area (LHA) to the dorsal raphe nucleus (DRN) on anxiety- and depression-like behaviors, intestinal motility, and visceral hypersensitivity in a mice model of IBS-D. The models of IBS-D were prepared by inducing chronic unpredictable mild stress (CUMS). RESULTS: Chemogenetic activation of the MCH neurons in the LHA could excite serotonin (5-HT) neurons in the DRN and induce anxiety- and depression-like behaviors and IBS-D-like symptoms, which could be recovered by microinjection of the MCH receptor antagonist SNAP94847 into the DRN. The mice model of IBS-D showed a reduction of 5-HT and brain-derived neurotrophic factor (BDNF) expression in the DRN, while an elevation of 5-HT and BDNF was observed in the colon through immunofluorescent staining, ELISA, and western blot analysis. SNAP94847 treatment in the DRN alleviated anxiety- and depression-like behaviors, improved intestinal motility, and alleviated visceral hypersensitivity responses by normalizing the 5-HT and BDNF expression in the DRN and colon. CONCLUSION: This study suggests that the activation of MCH neurons in the LHA may induce IBS-D symptoms via the DRN and that the MCH receptor antagonist could potentially have therapeutic effects.

In situ growth of copper-based energetic complexes on GO and an MXene to synergistically promote the thermal decomposition of ammonium perchlorate.

In this work, using tri(5-aminotetrazolium)triazine (H3TATT) as an energetic ligand, two new energetic complexes (ECs), Cu(HTATT)(H2O)2 (EC-Cu1) and [Cu3(TATT)2(H2O)2]n (EC-Cu2), have been synthesized under hydrothermal conditions. Their crystal structures, thermal decomposition behaviors and specific heat capacities were determined respectively. In addition, two ECs were combined with GO (graphene oxide) and an MXene (Ti3C2TX) respectively by an in situ growth strategy to obtain four carbon nanomaterials/EC composites, which were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The effects of two ECs and four composites on the thermal decomposition of AP were studied by differential scanning calorimetry (DSC). Among them, the sample containing 8 wt% composite (GO/EC-Cu2) has the best promoting effect on AP, causing the high temperature decomposition peak to overlap with the low temperature decomposition peak of AP, reducing the decomposition peak temperature of AP from 443.6 °C to 308.9 °C, and the heat release is up to 4875 J g-1. Compared with ECs acting solely on AP, composite materials have stronger synergistic and promoting effects. This study provides a new example of the synthesis of carbon nanomaterial/EC composites and the improvement of the performance of AP-based solid propellants.

Association of environmental polycyclic aromatic hydrocarbons exposure with periodontitis in NHANES 2009-2014: A mixtures approach.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) can invade and cause harm to the human body through various pathways, but there is currently little research on the relationship between mixed-PAHs exposure and periodontitis. The purpose of this study was to examine the effects of mixed-urinary PAHs exposure on periodontitis in adults in the United States. METHODS: The cross-sectional study included 2749 subjects selected from the National Health and Nutrition Examination Survey (NHANES) 2009-2014 cycles. A professional examination of the periodontal status was conducted to distinguish between periodontitis and non-periodontitis based on the Centers for Disease Control and Prevention/American Academy of Periodontology (CDC/AAP) case definition. Laboratory testing of urine samples was performed to obtain the levels of urinary PAHs. Pearson correlation coefficients were utilized to determine the degree of correlation between urinary PAHs, while weighted binary logistic regression and Bayesian kernel machine regression (BKMR) were employed to evaluate the relationship between urinary PAHs and periodontitis. RESULTS: In a single-exposure model, 3-hydroxyfluorene (OH-3F), 2-hydroxyfluorene (OH-2F), 1-hydroxyphenanthrene (OH-1Ph), and 2-hydroxyphenanthrene and 3-hydroxyphenanthrene (OH-2,3Ph) were positively associated with periodontitis risk. In the mixed-exposure model, BKMR analysis demonstrated that mixed exposure to urinary PAHs was positively associated with periodontitis, with OH-2F being the most critical factor for the overall mixed effects (posterior inclusion probability [PIP] = 0.98). Univariate exposure-response function and univariate effects analysis revealed a positive correlation between urinary OH-2F levels and periodontitis. CONCLUSIONS: The study reveals a significant positive correlation between exposure to mixed PAHs and periodontitis, with a particular emphasis on the pivotal role of OH-2F. Mitigating PAHs in the environment may serve as a preventive measure against periodontitis and alleviate its global public health burden.

Efficacy and immunological changes of sublingual immunotherapy in pediatric allergic rhinitis.

Background: Allergen-specific immunotherapy, including subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), improves the disease progression of allergic rhinitis (AR). SCIT and SLIT exhibit similar efficacy, but SLIT has less systemic reactions. However, few studies have investigated the underlying mechanisms of SLIT treatment. In this study, we explored the efficacy of SLIT under different treatment durations and immunological changes. Methods: This retrospective study was conducted from August 2017 to August 2022 in our hospital. A total of 314 children who underwent SLIT were divided into the following groups based on their treatment duration: the 1 year group (6 months-1 year), the 2 years group (1-2 years), and the 3 years group (2-3 years). The treatment efficacy was confirmed using a combined symptom and medication score (SMS). Multiple serum cytokines were measured using Luminex. Various immune cells in PBMCs were determined using flow cytometry. Results: The total nasal symptom score (TNSS), rescue medication score (RMS), and SMS of the 3 years group was significantly different from those of the 1 years and 2 years groups. At the end of the 2 years following cessation of SLIT, the following results were observed in the 3 years group: 1) the TNSS, RMS, and SMS had significantly improved, 2) the serum IL-10, TGF-beta, and IL-35 levels had increased significantly, and 3) the percentages of regulatory T cell, regulatory B cell, and follicular regulatory T cell increased significantly. Conclusion: Our results suggest that 3 years of SLIT is necessary for long-term effects and continued immunological changes.

Increased GABAergic projections in the paraventricular nucleus regulate colonic hypersensitivity via oxytocin in a rat model of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is characterized by gastrointestinal dysmotility and visceral hyperalgesia, and the impaired brain-gut axis is accepted as a crucial cause for the onset of IBS. The objective of this study is to investigate the effects of the adaptive changes in the central neural system induced by stress on IBS-like syndromes in rats. Long-term water avoidance stress (WAS) was used to prepare IBS animals. The changes in neuronal excitation and GABA expression were shown by immunohistochemistry. The mRNA and protein expressions of neurotransmitters were detected with Quantitative reverse-transcription PCR (qRT-PCR) and Enzyme-linked immunosorbent assay (ELISA). The intestinal transit time, fecal moisture content, and abdominal withdrawal reflex scores of rats were recorded to monitor intestinal motility and visceral hyperalgesia. In the WAS-treated rats with enhanced intestinal motility and visceral hypersensitivity, more GABAergic projections were found in the paraventricular nucleus (PVN) of the hypothalamus, which inhibited the firing rate of neurons and decreased the expression of oxytocin. Exogenous oxytocin improved gut motility and decreased AWR scores. The inhibition of oxytocin by the adaptive GABAergic projection in the PVN might be an important mediator of IBS, which indicates a potential novel therapeutic target.

Regulation of the central amygdala on intestinal motility and behavior via the lateral hypothalamus in irritable bowel syndrome model mice.

BACKGROUND: Impaired bidirectional communication between the gastrointestinal tract and the central nervous system (CNS) is closely related to the development of irritable bowel syndrome (IBS). Studies in patients with IBS have also shown significant activation of the hypothalamus and amygdala. However, how neural circuits of the CNS participate in and process the emotional and intestinal disorders of IBS remains unclear. METHODS: The GABAergic neural pathway projecting from the central amygdala (CeA) to the lateral hypothalamus (LHA) in mice was investigated by retrograde tracking combined with fluorescence immunohistochemistry. Anxiety, depression-like behavior, and intestinal motility were observed in the water-immersion restraint stress group and the control group. Furthermore, the effects of the chemogenetic activation of the GABAergic neural pathway of CeA-LHA on behavior and intestinal motility, as well as the co-expression of orexin-A and c-Fos in the LHA, were explored. KEY RESULTS: In our study, Fluoro-Gold retrograde tracking combined with fluorescence immunohistochemistry showed that GABAergic neurons in the CeA were projected to the LHA. The microinjection of the gamma-aminobutyric acid (GABA) receptor antagonist into the LHA relieved anxiety, depression-like behavior, and intestinal motility disorder in the IBS mice. The chemogenetic activation of GABAergic neurons in the CeA-LHA pathway led to anxiety, depression-like behavior, and intestinal motility disorder. In addition, GABAergic neurons in the CeA-LHA pathway inhibited the expression of orexin-A in the LHA, and orexin-A was co-expressed with GABAA receptors. CONCLUSIONS & INFERENCES: The CeA-LHA GABAergic pathway might participate in the occurrence and development of IBS by regulating orexin-A neurons.

High density lipoprotein inhibited group II innate lymphoid cells proliferation and function in allergic rhinitis.

BACKGROUND: More and more studies had suggested that dyslipidemia was closely related to allergic diseases. High density lipoprotein (HDL) often plays anti-inflammatory and anti-oxidative roles by suppressing immune cell chemotaxis and activation. We aimed to explore the role of HDL in the regulation of group II innate lymphoid cells (ILC2) in allergic rhinitis (AR). METHODS: The blood lipid levels and their correlation with symptom scores of 20 AR subjects and 20 controls were analyzed. Purified ILC2 were stimulated by HDL and cytokines production were examined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The mRNA levels of GATA binding protein 3(GATA3) and retinoid-related orphan receptor α (RORα) expressed by ILC2 were detected using reverse transcription polymerase chain reaction (RT-PCR). RESULTS: HDL level was significantly lower in AR than controls and correlated with the symptom scores. The serum HDL levels were negatively related to the increased number of ILC2, IL-5+ ILC2, and IL-13+ ILC2 in AR patients. HDL decreased the number of ILC2 and type II cytokines levels significantly by inhibiting expression of GATA3 and RORα. CONCLUSIONS: Our data provide preliminary evidence that HDL may play a negative role in ILC2 inflammation in AR, suggesting that HDL may serve as promising treatment target in AR.

Dynamic Metal-Iodide Bonds in a Tetracoordinated Cadmium-Based Metal-Organic Framework Boosting Efficient CO2 Cycloaddition under Solvent- and Cocatalyst-Free Conditions.

Due to the inherent thermodynamic stability and kinetic inertness of CO2, heterogeneous catalytic conversion of CO2 to cyclic carbonates often requires harsh operating conditions, high temperature and high pressure, and the addition of cocatalysts. Therefore, the development of efficient heterogeneous catalysts under cocatalyst-free and mild conditions for CO2 conversion has always been a challenge. Herein, an infrequent tetracoordinated Cd-MOF was synthesized and used to catalyze CO2 cycloaddition reactions efficiently without the addition of any cocatalyst, and its catalytic mechanism was systematically investigated through a series of experiments, including fluorescence analysis, X-ray photoelectron spectroscopy, microcalorimetry, and density functional theory (DFT) calculation. Cd-MOF features a 3D supermolecule structure with 1D 11.6 × 7.7 Å2 channels, and the abundant Lewis acid/base and I- sites located in the confined channel boost efficient CO2 conversion with a maximum yield of 98.2% and a turnover number value of 1080.11 at 60 °C and 0.5 MPa, far surpassing most pristine MOF-based catalytic systems. A combined experimental and DFT calculation demonstrates that the exposed Cd(II) Lewis acid sites rapidly participate in coordination to activate the epoxides, and the resulting large steric hindrance facilitates leaving of the coordinated iodide ions in a reversibly dynamic fashion convenient for the rate-determining step ring-opening as a strong nucleophile. Such a pristine MOF catalyst with self-independent catalytic ring-opening overcomes the complicated operation limitation of the traditional cocatalyst-free MOF systems based on encapsulating/postmodifying cocatalysts, providing a whole new strategy for the development of simple, green, and efficient heterogeneous catalysts for CO2 cycloaddition.

Conjugated linoleic acid ameliorates hepatic steatosis by modulating intestinal permeability and gut microbiota in ob/ob mice.

Background: Conjugated linoleic acid (CLA) is an effective supplement for reducing fat mass, but its effect on hepatic steatosis remains controversial. Objective: This study aims to evaluate the effect of CLA on liver fat accumulation, inflammation, gut microbiome, and intestinal barrier integrity. Design: Wild-type (WT) mice and ob/ob (OB) mice were randomly divided into four groups according to the treatment with/without 1% CLA: WT, WT mice treated with CLA (WT-CLA), OB, and OB mice treated with CLA (OB-CLA). Lipid metabolism and hepatic fat accumulation were evaluated by changes in histological and biochemical parameters. Gene expressions related to liver inflammation and intestinal barrier integrity were examined. The effect of CLA on the gut microbiota population was investigated. Results: The body weight, fatty tissue mass, and serum lipid levels of the WT-CLA group and OB-CLA group were separately lower than those of the WT group and OB group, but the livers of the WT-CLA group had more fatty lipids, higher triglyceride properties, and saturated fatty acid (FA) composition than those of the WT group, which was contrary to the effect of CLA on OB mice. Real time quantitative PCR results showed that CLA increased hepatic inflammation and intestinal permeability in the WT mice, while it significantly decreased the mRNA expression of liver TNF-α, IFN-γ, and IL-1ß and markedly ameliorated intestinal tight junction proteins in the OB mice. The gut microbiota testing indicated a higher abundance of beneficial bacteria (e.g., Lachnoclostridium, Roseburia, Dubosiella, Oscillibacter, and Anaerostipes) and a lower abundance of pro-inflammatory bacteria (e.g., Tyzzerella and Alistipes) in the OB-CLA group than those of the OB group. Correlation analysis suggested that gut microbiota correlated with liver inflammation, intestinal permeability, and hepatic FA composition. Conclusion: CLA potentially contributed to ameliorating hepatic steatosis in OB mice via modulating liver inflammation, intestinal permeability, and gut microbiota, which suggests CLA is more suitable for people with obesity or overweight.

Associations of Household Solid Fuel Use With Falls and Fall-Related Injuries in Middle-Aged and Older Population in China: A Cohort Study.

Objective: This study evaluated the associations of solid fuels with incidence of falls and fall-related injuries. Methods: Data were taken from wave 1∼4 of the China Health and Retirement Longitudinal Study, including 15,651 participants aged 45 years and older. Modified Poisson regression was used to examine the associations of solid fuels with falls and fall-related injuries. Results: Modified Poisson regression analysis showed that solid fuels users for cooking had an increasing incidence of falls and fall-related injuries, with RR of 1.211 (95% CI: 1.124, 1.305) and 1.248 (95% CI: 1.107, 1.408); for heating had an incidence, with RR of 1.178 (95% CI: 1.062, 1.306) and 1.134 (95% CI: 0.963, 1.335); combined for cooking and heating, with RR of 1.247 (95% CI: 1.105, 1.408) and 1.185 (95% CI: 0.982, 1.431). Conclusion: Our study suggests that solid fuel use is associated with a higher incidence of falls and fall-related injuries among adults aged 45 years and older in China. It is necessary to restrict solid fuel use to reduce household air pollution and make stronger environmental protection policies to improve household environment.

Calcium-sensing receptor (CaSR) agonist R568 inhibits small intestinal motility of mice through neural and non-neural mechanisms.

Gastrointestinal motility (GI) disorder causes symptoms such as dyspepsia, abdominal distention, and constipation and severely affects quality of life. The calcium (Ca2+)-sensing receptor (CaSR) expressed in the digestive tract can be activated by amino acids and participates in GI motility regulation. This study is designed to explore the effect and underlying mechanism of CaSR agonist R568 on the small intestine motility of mice in vivo and ex vivo. R568 was given to male C57BL/6 mice by gavage or incubated with isolated jejunum and ileum segments to observe its effects on GI motility and the involved neurons, neurotransmitters and hormones were detected by fluorescence immunohistochemistry and enzyme-linked immunosorbent assays. The in vivo results showed that the intestinal propulsive rate reduced in response to oral intake of R568. R568 treatment increased the numbers of nitric oxide synthase-positive neurons and nitric oxide release but decreased the choline acetyl transferase-positive neurons and acetylcholine release in the myenteric plexuses. R568 increased the secretion of cholecystokinin in the intestinal tissues and serum but had no effect on the secretion of glucagon like peptide-1. Ex vivo results showed that R568 inhibited the contractility of intestinal strips from the jejunum and ileum. Nitric oxide synthase (NOS) inhibitor L-nitroarginine methyl ester (L-NAME), M-receptor antagonist-atropine, and tetrodotoxin (TTX) failed to block the effect of R568. CaSR co-expressed with interstitial cells of Cajal (ICCs) in the myenteric plexus suggests the possibility that ICCs mediated the effect of R568. Our findings demonstrate that CaSR activation inhibited intestinal motility, and both the enteric nervous system and non-neural mechanism are involved in this process.

Microglia and macrophage exhibit attenuated inflammatory response and ferroptosis resistance after RSL3 stimulation via increasing Nrf2 expression.

BACKGROUND: Many neurological diseases involve neuroinflammation, during which overproduction of cytokines by immune cells, especially microglia, can aggregate neuronal death. Ferroptosis is a recently discovered cell metabolism-related form of cell death and RSL3 is a well-known inducer of cell ferroptosis. Here, we aimed to investigate the effects of RSL3 in neuroinflammation and sensitivity of different type of microglia and macrophage to ferroptosis. METHODS: Here, we used quantitative RT-PCR analysis and ELISA analysis to analyze the production of proinflammatory cytokine production of microglia and macrophages after lipopolysaccharides (LPS) stimulation. We used CCK8, LDH, and flow cytometry analysis to evaluate the sensitivity of different microglia and macrophages to RSL3-induced ferroptosis. Western blot was used to test the activation of inflammatory signaling pathway and knockdown efficiency. SiRNA-mediated interference was conducted to knockdown GPX4 or Nrf2 in BV2 microglia. Intraperitoneal injection of LPS was performed to evaluate systemic inflammation and neuroinflammation severity in in vivo conditions. RESULTS: We found that ferroptosis inducer RSL3 inhibited lipopolysaccharides (LPS)-induced inflammation of microglia and peritoneal macrophages (PMs) in a cell ferroptosis-independent manner, whereas cell ferroptosis-conditioned medium significantly triggered inflammation of microglia and PMs. Different type of microglia and macrophages showed varied sensitivity to RSL3-induced ferroptosis. Mechanistically, RSL3 induced Nrf2 protein expression to inhibit RNA Polymerase II recruitment to transcription start site of proinflammatory cytokine genes to repress cytokine transcription, and protect cells from ferroptosis. Furthermore, simultaneously injection of RSL3 and Fer-1 ameliorated LPS-induced neuroinflammation in in vivo conditions. CONCLUSIONS: These data revealed the proinflammatory role of ferroptosis in microglia and macrophages, identified RSL3 as a novel inhibitor of LPS-induced inflammation, and uncovered the molecular regulation of microglia and macrophage sensitivity to ferroptosis. Thus, targeting ferroptosis in diseases by using RSL3 should consider both the pro-ferroptosis effect and the anti-inflammation effect to achieve optimal outcome.

Efficacy of Sublingual Immunotherapy in Allergic Rhinitis Children during Coronavirus Disease 2019.

BACKGROUND: Sublingual immunotherapy (SLIT) had good effectiveness for children with allergic rhinitis (AR). However, no studies explored the effect of persistent allergen exposure on SLIT treatment. Coronavirus disease 2019 (COVID-19) restricts outdoor activities of children significantly. We aimed to evaluate the effectiveness of SLIT during this special period. METHODS: A total of 335 AR children who sensitize to house dust mite (HDM) undergoing SLIT were recruited in this study. The clinical effectiveness and safety were evaluated at different time points using symptom and medication scores. The serum total IgE and specific IgE (sIgE) at different time points were detected by using the Unicap system. RESULTS: The total nasal symptoms score (TNSS) and total medication score (TMS) during the epidemic of COVID-19 increased significantly compared with the same period last year (p < 0.05), despite that they were still significantly lower than baseline levels (p < 0.05). The occurrence of adverse reactions at different time points had no significant differences. We also found that the family of the good response group had more frequent bedding cleaning. Both the tIgE and sIgE levels had no significant changes during SLIT treatment. CONCLUSION: Our results suggest that continuous HDM exposure reduced the effectiveness of SLIT, whereas effective reduction of HDM levels by frequent bed cleaning will be helpful during the SLIT treatment.

An efficient cell culture system for the studies of heterogeneous astrocytes: Time gradient digestion.

BACKGROUND: Astrocytes are the most abundant glial cell type in mammal brain, but there exists a lot of unknown in cell development and cell function. We aim to establish an astrocytes culture system for obtaining highly enriched primary astrocytes from the neonatal mouse brain and separating Aldh1l1+Gfap- and Aldh1l1+Gfap+ cells. NEW METHOD: C57BL/J6 mouse pups at postnatal 1-4 days were used for cell preparation. Brain cortex was collected and digested with 0.25% trypsin followed by 0.5 mg/ml DNase. Cells were plated on PDL-coated flasks. After 8-10 days culture, cells were shaken at 260 rpm for 4 h at 37 â„ƒ to remove oligodendrocytes and microglia cells. Time gradient digestion was performed to obtain astrocyte subtypes. The digestion time was 0-2 min and 2-4 min, and 4-6 min. Flow cytometry, Immunostaining, CCK-8 assay and EdU staining was carried out to investigate the purity of the astrocytes, the ability of cell proliferation and to identify different subtypes. RESULTS: After shaking, percentage of oligodendrocytes significantly decreased from 22.6 ± 3.6% to 7.4 ± 1.4% (CNPase+ cells) and from 4.36 ± 0.6% to 0.75 ± 0.2% (Pdgfrα+ cells) while percentage of microglia cells reduced from 4.4 ± 0.2% to 0.6 ± 0.2%. Aldh1l1+Gfap- astrocytes were the dominant cell types in 0-2 min group while Aldh1l1+Gfap+ astrocytes were the dominant cell types in 2-4 min group. Moreover, compared with Aldh1l1+Gfap+ astrocytes, Aldh1l1+Gfap- astrocytes had a higher proliferative ability. COMPARISON WITH EXISTING METHODS: Aldh1l1+Gfap- and Aldh1l1+Gfap+ cells were separated. The percentage of residual Tmem119 + and Gfap+ cells showed no significant difference. However, the percentage of Pdgfrα+ cells were significant decreased, and the time consuming of the new system was lower. The astrocytes acquired possess higher viability. CONCLUSIONS: A new astrocytes culture system with time gradient digestion was established. Highly enriched primary astrocytes from the neonatal mouse brain were obtained with short shaking time. Aldh1l1+Gfap- and Aldh1l1+Gfap+ cells were separated by different digestion condition. This system has advantages of high efficiency and low cost, which deserves promising application in management of astrocytes research in central nerve system.

Tailoring Electronic Structure and Size of Ultrastable Metalated Metal-Organic Frameworks with Enhanced Electroconductivity for High-Performance Supercapacitors.

Utilization of metal-organic frameworks (MOFs) as electrodes for energy storage/conversion is challenging because of the low chemical stability and poor electrical conductivity of MOFs in electrolytes. A nanoscale MOF, Co0.24 Ni0.76 -bpa-200, possessing ultrahigh stability with uncommon semiconductor behavior (σ=4.2×10-3  S m-1 ) was fabricated. The MOF comprises a robust hydrophobic paddlewheel and an optimized Co/Ni ratio, with consequent control over MOF size and the degree of conjugation of the coligand. A DFT study revealed that appropriate Ni2+ doping reduces the activation energy of the system, thus providing a higher carrier concentration, and the strongly delocalized N-donor ligand notably increases the metal-ligand orbital overlap to achieve efficient charge migration, leading to continuous through-bond (-CoNi-N-CoNi-)∞ conduction paths. These structural features endow the MOF with a good cycling stability of 86.5 % (10 000 cycles) and a high specific capacitance of 1927.14 F g-1 among pristine MOF-based electrodes.

High temperature quantum tunnelling of magnetization and thousand kelvin anisotropy barrier in a Dy2 single-molecule magnet.

We report here a dinuclear DyIII iodine-bridged single-molecule magnet self-assembled by cis/trans coordination chemistry that displays a large anisotropy barrier of ca. 1300 K and a hysteresis opening temperature of 16 K. High temperature quantum tunnelling of magnetization is observed up to 56 K in zero-field and explained by the combination of the large anisotropy barrier and the local transverse field at the trans site. The results provide a model for thorough understanding of the effect of electronic structure on the magnetic behavior of lanthanide complexes.

Improved Detonation Performance Via Coordination Substitution: Synthesis and Characterization of Two New Green Energetic Coordination Polymers.

In this work, a new energetic coordination polymer (ECP), [Cu(HBTI)(H2O)]n (1) (H3BTI = 4,5-bistetrazole-imidazole), was synthesized by a hydrothermal method. Due to the existence of coordination water molecules in 1, however, its energy density was limited, which led to the insufficient detonation performance. To further improve its detonation performance, [Cu(H2BTI)(NO3)]n (2) was then obtained by substituting the coordinated water molecule in 1 with nitrate through the coordination substitution reaction under acidic conditions. The structures of two ECPs were respectively characterized using X-ray single-crystal diffraction, and the theoretical density of 2 (2.227 g·cm-3) was greater than 1 (1.851 g·cm-3). Thermogravimetric analyses showed that 2 has a one-step rapid weight loss process compared with the two-step slow weight loss process of 1. The theoretical calculations indicated that the detonation performances of 2 were better than those of 1. Moreover, the promotion effects of two ECPs on the combustion decomposition of ammonium perchlorate were studied using a differential scanning calorimetry method.

GABAergic neurons in the nucleus accumbens regulate hedonic food intake via orexin-A expression in the lateral hypothalamus.

OBJECTIVES: To investigate the regulatory effects of the nucleus accumbens (NAcSh)-lateral hypothalamus (LHA) GABAergic neural pathway on palatable food (PF) intake via orexin-A expression in diet-induced obesity (DIO) rats. MATERIALS AND METHODS: NAcSh-LHA GABAergic pathways were observed by fluorogold retrograde tracing combined with fluorescence immunohistochemistry, and the regulatory effects of this neural pathway on PF intake were detected after 1) microinjection of GABA-A receptor agonist muscimol (MUS) or antagonist bicuculine (BIC) into LHA, 2) electrical stimulation NAcSh, and 3) blocking the orexin-A receptor by icv SB334867. RESULTS: Compared with rats on a normal diet (ND), NAcSh-LHA GABAergic neurons in the DIO rats were significantly decreased, and orexin-A expression in LHA significantly increased (P<0.05). Microinjection of MUS into LHA significantly decreased the PF intake in both ND and DIO rats (P<0.05), and BIC could markedly increase the PF intake in the ND rats (P<0.05), but not the DIO rats (P>0.05). After NAcSh electrical stimulation or SB334867 ICV injection, the PF intake was significantly decreased in the DIO rats (P<0.05), and there was no significant difference after preadministration of BIC into LHA (P>0.05). CONCLUSION: This GABAergic pathway could regulate the expression of orexin-A in LHA and PF intake. Orexin-A neurons in LHA of DIO rats might be less sensitive to GABAergic signals and may consequently lead to more hedonic food intake.