Higher-order dynamic effects of uncertainty risk under thick-tailed stochastic volatility.

Sudden and uncertain events often cause cross-contagion of risk among various sectors of the macroeconomy. This paper introduces the stochastic volatility shock that follows a thick-tailed Student's t-distribution into a high-order approximate dynamic stochastic general equilibrium (DSGE) model with Epstein-Zin preference to better analyze the dynamic effect of uncertainty risk on macroeconomics. Then, the high-dimensional DSGE model (DSGE-SV-t) is developed to examine the impact of uncertainty risk on the transmission mechanism among macroeconomic sectors. The empirical research found that uncertainty risk generates heterogeneous impacts on macroeconomic dynamics under different inflation levels and economic states. Among them, a technological shock has the strongest impact on employment and consumption channels. The crowding-out effect of a fiscal policy stimulus on consumption and private investments is relatively weakened when considering uncertainty risk but is more pronounced during periods of high inflation. Uncertainty risk can partly explain the decline in investments and the increase in interest rates and employment rates, given the impact of an agent's risk preferences. Compared with external economic conditions, the inflation factor has a stronger impact on the macro transmission mechanism caused by uncertainty risk.

[Phagocytosis of microglia in neurodegenerative diseases].

With the acceleration of the aging society, neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), have become a rapidly growing global health crisis. Recent studies have indicated that microglia-neuron interactions are critical for maintaining homeostasis of the central nervous system. Genome-Wide Association Studies and brain imaging studies have suggested that microglia are activated in early stage of neurodegenerative diseases. Microglia are specialized phagocytes in the brain. The discovery of a new phagocytic pathway, trogocytosis, suggests that there is a close interaction between microglia and surviving neurons. In this review, we summarize the important roles of microglia in neurodegenerative diseases, and further analyze the functions and molecular mechanisms of microglia phagocytosis and trogocytosis.

Effects of auricular acupressure on depression in stroke patients: A single-blind randomized controlled trial.

BACKGROUND AND PURPOSE: Post-stroke depression (PSD) has an important impact on rehabilitation, motor recovery, daily activities, social and interpersonal life, and mortality. This study aimed to evaluate the effects of auricular acupressure (AurPrs) on depression in PSD patients. MATERIALS AND METHODS: Fifty-six PSD patients were recruited and randomly assigned to the AurPrs group (receiving AurPrs treatment) or the sham group (receiving sham AurPrs treatment). The outcome was measured by the 17-item Hamilton Rating Scale for Depression (HAMD-17), Zung Self-Rating Depression Scale (SDS), and World Health Organization Quality of Life Brief Version (WHOQOL-BREF). RESULTS: There was a statistically significant difference in HAMD-17 score, SDS score and WHOQOL-BREF score between both groups before and after treatment (P < 0.01). The improvement of the AurPrs group was more obvious than that of the sham group (P < 0.05). CONCLUSION: AurPrs could help to reduce depression levels and improve the quality of life in patients with PSD.

[Biodegradation of Algae-derived Organic Matter (I-DOM) from Lake Taihu].

A large amount of intracellular dissolved organic matter (I-DOM) is released during the senescent phase of phytoplankton cultures. This research investigated the bio-incubation of I-DOM of cyanobacteria in Lake Taihu under various temperatures (20, 25, and 30℃) and I-DOM initial concentrations (5, 10, and 20 mg·L-1) with the aid of ultraviolet-visible spectroscopy (UV-Vis) and three-dimensional fluorescence matrix-parallel factor (EEM-PARAFAC). I-DOM was effectively degraded during the incubation. After 14 days, the DOC removal ratio was 50% ~74%. A tryptophan-like component (C1), a ubiquitous humic-like component (C2), and two microbially-derived humic-like components (C3 and C4) contributed 80.0%, 16.0%, 3.7%, and 0.3% to the initial I-DOM, respectively. During the bio-degradation, these components are not only consumed but also produced. C1 decreased during the incubation, while C3 and C4 increased at the beginning of biodegradation and then decreased. The change trend of C2 was complicated, i.e., it decreased firstly and then increased, but decreased again after 7 days. The changes in the optical indices of Sr, E2:E3 and HIX revealed that the molecular weight of DOM increased, and the aromaticity was enhanced during degradation. The reaction temperature and the initial concentration of I-DOM did not change the trend of the PARAFAC components. The temperature of 25℃ was the most suitable for I-DOM bio-degradation. Additionally, the degradation of I-DOM was enhanced with the increase in the initial concentration of I-DOM. Combined with our study on the photodegradation of I-DOM, the possible fate of I-DOM in Lake Taihu was proposed. The tryptophan-like compound could be effectively degraded, while the humic-like components could not be degraded completely. These humic-like components would potentially settle through adsorption or coprecipitation with metal substances. These results are helpful to understand the fate of I-DOM released by a cyanobacteria bloom in Lake Taihu.

VCAM1 Labels a Subpopulation of Neural Stem Cells in the Adult Hippocampus and Contributes to Spatial Memory.

Active neural stem cells (aNSCs) and quiescent neural stem cells (qNSCs) are two distinct subpopulations found in the adult hippocampal dentate gyrus (DG). However, to date, no cell surface marker has been established to identify and profile qNSCs in the adult hippocampus. Here, we identified expression of vascular cell adhesion molecule 1 (VCAM1) on the cell surface of NSCs, through which we identified a previously unrecognized subpopulation of NSCs in the adult mouse DG. Interestingly, most VCAM1-expressing NSCs were largely quiescent. By injecting virus into Ai14 reporter mice to conduct lineage tracing in the adult DG, we confirmed that VCAM1-expressing cells were multipotent and capable of generating neurons and astrocytes. Furthermore, depletion of Vcam1 during the embryonic or adult stage impaired spatial learning and memory in mice, accompanied by a reduced number of radial glial-like cells and proliferating NSCs in the subgranular zone of Vcam1 knockout mice.

Mutations in C1orf194, encoding a calcium regulator, cause dominant Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease is a hereditary motor and sensory neuropathy exhibiting great clinical and genetic heterogeneity. Here, the identification of two heterozygous missense mutations in the C1orf194 gene at 1p21.2-p13.2 with Charcot-Marie-Tooth disease are reported. Specifically, the p.I122N mutation was the cause of an intermediate form of Charcot-Marie-Tooth disease, and the p.K28I missense mutation predominately led to the demyelinating form. Functional studies demonstrated that the p.K28I variant significantly reduced expression of the protein, but the p.I122N variant increased. In addition, the p.I122N mutant protein exhibited the aggregation in neuroblastoma cell lines and the patient's peroneal nerve. Either gain-of-function or partial loss-of-function mutations to C1ORF194 can specify different causal mechanisms responsible for Charcot-Marie-Tooth disease with a wide range of clinical severity. Moreover, a knock-in mouse model confirmed that the C1orf194 missense mutation p.I121N led to impairments in motor and neuromuscular functions, and aberrant myelination and axonal phenotypes. The loss of normal C1ORF194 protein altered intracellular Ca2+ homeostasis and upregulated Ca2+ handling regulatory proteins. These findings describe a novel protein with vital functions in peripheral nervous systems and broaden the causes of Charcot-Marie-Tooth disease, which open new avenues for the diagnosis and treatment of related neuropathies.

The Role of Group II Metabotropic Glutamate Receptors in the Striatum in Electroacupuncture Treatment of Parkinsonian Rats.

AIMS: Glutamatergic transmission may play a critical role in the pathogenesis of Parkinson's disease (PD). Electroacupuncture (EA) has been demonstrated to effectively alleviate PD symptoms. In this study, a potential glutamate-dependent mechanism underlying the therapeutic action of EA was investigated. METHODS: The effects of EA stimulation on motor behaviors, dopamine contents, glutamate release, and group II metabotropic glutamate receptor (mGluR2/3) expression in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats were examined. RESULTS: Unilateral 6-OHDA lesions of the nigrostriatal system caused a marked increase in glutamate content in the ipsilateral cortex and striatum. mGluR2/3 protein expression and mGluR3 mRNA expression were reduced in the striatum. Noticeably, prolonged EA stimulation at 100 Hz significantly reversed these changes in the striatal glutamate system. Behaviorally, EA improved the motor deficits induced by 6-OHDA lesions. Intrastriatal infusion of an mGluR2/3 antagonist APICA blocked the improving effect of EA. CONCLUSIONS: These data collectively demonstrate that the group II mGluR-mediated glutamatergic transmission in the striatum is sensitive to dopamine depletion and may serve as a substrate of EA for mediating the therapeutic effect of EA in a rat model of PD.

The E3 Ubiquitin Ligase c-Cbl Inhibits Microglia-Mediated CNS Inflammation by Regulating PI3K/Akt/NF-κB Pathway.

BACKGROUND: Microglia-mediated inflammation may play an important role in the pathophysiology progression of neurodegenerative diseases, such as Parkinson's disease (PD), but the molecular mechanisms are poorly understood. AIMS: This study sought to determine whether E3 ubiquitin ligase c-Cbl plays a role in the brain inflammation and to explore the relevant molecular mechanism. METHODS: After BV2 microglial cells and c-Cbl-deficient mice were treated with lipopolysaccharide (LPS), neuroinflammation and microglial activation were evaluated by immunohistochemistry, ELISA and Western blot. We further investigated the possible mechanism of c-Cbl in regulating microglial activation. RESULTS: Here, we showed that the E3 ubiquitin ligase c-Cbl had high expression in brain tissues including substantia nigra pars compacta (SNc), striatum and hippocampus, and it was abundantly expressed in microglia. Systemic LPS administration resulted in more severe microglial activation in CNS and increased expression of brain proinflammatory factors (TNF-α, IL-6, IL-1ß and MCP-1) in c-Cbl knockout mice than wild type mice (WT). Downregulation of c-Cbl expression with c-Cbl siRNA in BV-2 microglial cells demonstrated a more robust increase in the proinflammatory factors release and NF-κB p65 nuclear translocation than that in control siRNA. Interestingly, Akt phosphorylation induced by LPS was also significantly augmented after c-Cbl knockdown. Moreover, blockade of PI3K/Akt activation by LY294002 significantly reduced inflammation response and NF-κB p65 nuclear translocation. CONCLUSION: In sum, c-Cbl inhibits expression of LPS-stimulated proinflammatory cytokines and chemokines in microglia. We demonstrate an unprecedented role for c-Cbl in microglia-mediated neuroinflammation involving PI3K/Akt/NF-κB pathway.

Enhanced antidepressant-like effects of electroacupuncture combined with citalopram in a rat model of depression.

Currently, antidepressants are the dominative treatment for depression, but they have limitations in efficacy and may even produce troublesome side effects. Electroacupuncture (EA) has been reported to have therapeutic benefits in the treatment of depressive disorders. The present study was conducted to determine whether EA could enhance the antidepressant efficacy of a low dose of citalopram (an SSRI antidepressant) in the chronic unpredictable stress-induced depression model rats. Here, we show that a combined treatment with 2 Hz EA and 5 mg/kg citalopram for three weeks induces a significant improvement in depressive-like symptoms as detected by sucrose preference test, open field test, and forced swimming test, whereas these effects were not observed with either of the treatments alone. Further investigations revealed that 2 Hz EA plus 5 mg/kg citalopram produced a remarkably increased expression of BDNF and its receptor TrkB in the hippocampus compared with those measured in the vehicle group. Our findings suggest that EA combined with a low dose of citalopram could produce greater therapeutic effects, thereby, predictive of a reduction in drug side effects.

Tenuigenin attenuates α-synuclein-induced cytotoxicity by down-regulating polo-like kinase 3.

BACKGROUND AND AIMS: Tenuigenin (Ten) is a Chinese herbal extract with antioxidative and antiinflammatory effects on toxin-induced cell models of Parkinson's disease (PD); however, its effects on α-synuclein toxicity-based PD models remain unknown. α-synuclein hyperphosphorylation is a key event in PD pathogenesis and potential target of therapeutic interventions. We tested whether Ten alleviates α-synuclein-induced cytotoxicity via reducing kinases that phosphorylate α-synuclein. METHODS: SH-SY5Y cells transiently transfected with wild-type or A53T mutant α-synuclein were used to evaluate the effect of Ten on the levels of α-synuclein phosphorylation-related kinases. Cells treated with 10 µM Ten for 24 h were measured for viability (proliferation and apoptosis assays) and cellular proteins harvested and fractioned. The levels of total and phosphorylated α-synuclein and five associated kinases (polo-like kinase [PLK] 1-3, casein kinase [CK] 1-2) were evaluated by Western blotting. RESULTS: Overexpression of either wild-type or A53T mutant α-synuclein decreased cell viability and increased α-synuclein phosphorylation. Ten treatment-protected cells from this α-synuclein-induced toxicity and dramatically reduced α-synuclein phosphorylation and PLK3 (but not other kinase) levels. CONCLUSION: In α-synuclein cell model of PD, Ten is effective in attenuating α-synuclein-induced toxicity and α-synuclein phosphorylation probably via targeting PLK3, suggesting it could be an efficient therapeutic drug to treat α-synuclein-related neurodegeneration.

Chiral recognition of a 3D chiral nanoporous metal-organic framework.

Some racemates including alcohol, ketone, flavone, phenol, base, and amide racemates etc. were successfully separated by using a 3D chiral nanoporous metal-organic framework (MOF) as a new chiral stationary phase in HPLC. The experimental results show that the chiral MOF possesses excellent recognition ability for various racemates, and indicate that enantioseparation on the chiral MOF column is practicable.

A DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, exacerbates neurotoxicity and upregulates Parkinson's disease-related genes in dopaminergic neurons.

AIMS: To investigate effects of DNA methyltransferase (DNMT) inhibitors on dopaminergic neurons and its underlied mechanism. METHODS: The DNMT inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) was tested in cultured dopaminergic cells. Cell viability and apoptosis were assayed with 5-aza-dC alone. Neurotoxicity of 1-methyl-4-phenylpyridinium (MPP(+) ), 6-hydroxydopamine or rotenone was also assayed with 5-aza-dC pretreatment. And mRNA levels of several key PD-related genes were examined by semiquantitative RT-PCR. Furthermore, CpG methylation of α-synuclein promoter was examined by bisulfite sequencing. RESULTS: 5-aza-dC resulted in decreased cell viability and increased apoptosis in dopaminergic neuronal cells. Pretreatment with 5-aza-dC exacerbated neurotoxic damage to dopaminergic neurons induced by MPP(+) , 6-hydroxydopamine or rotenone. 5-aza-dC also induced transcriptional upregulation of the key PD-related genes tyrosine hydroxylase and α-synuclein. And demethylation of CpG in α-synuclein promoter was also induced by 5-aza-dC and MPP(+) . CONCLUSIONS: This DNMT inhibitor might influence pathogenesis of PD. And demethylation induced by DNMT inhibitor might contribute to dopaminergic neuron death, by increasing vulnerability of dopaminergic neurons to neurotoxins and by misregulating transcription of key PD-related genes. Our data also suggested DNMT inhibitors may cause multiple effects on dopaminergic neurons.

The cortical and striatal gene expression profile of 100 hz electroacupuncture treatment in 6-hydroxydopamine-induced Parkinson's disease model.

Electroacupuncture (EA), especially high-frequency EA, has frequently been used as an alternative therapy for Parkinson disease (PD) and is reportedly effective for alleviating motor symptoms in patients and PD models. However, the molecular mechanism underlying its effectiveness is not completely understood. To implement a full-scale search for the targets of 100 Hz EA, we selected rat models treated with 6-hydroxydopamine into the unilateral MFB, which mimic end-stage PD. High-throughput microarray analysis was then used to uncover the regulated targets in the cortex and striatum after 4-week EA treatment. In the differentially regulated transcripts, the proportion of recovered expression profiles in the genes, the functional categories of targets in different profiles, and the affected pathways were analyzed. Our results suggested that the recovery of homeostasis in the transcript network and many regulated functional clusters in the cortex and striatum after EA treatment may contribute to the behavioral improvement of PD rats.

[Determination of nicacid and its metabolites in human plasma by HPLC-MS/MS].

OBJECTIVE: To develop a sensitive HPLC-MS/MS method for the determination of nicacid and its metabolites in human plasma. METHODS: The assay was conducted with an API 3000 LC-MS/MS system comprising of a Genimi C18 column (50 x 3.00 mm, 3 microm), and an eluate of 0.1% acetic acid-methanol-isopropyl alcohol (98: 1:1), and flow rate was 0.2 mL/min. Acetonitrile was used to precipitate protein from the plasma samples. The loading samples contained the residue from the supernatant that were dissolved in the eluate solution and rinsed by dichloromethane was used as the loading samples. The ion pairs of m/z 124.1-->80.0, m/z 123.1-->80.0, m/z 181.1-->135.0 and m/z 138.1-->92.0 were used to quantify nicacid, niacinamide, nicotinuric acid and 6-methyl nicotinic acid (IS), respectively. RESULTS: The standard curves of nicacid, niacinamide and nicotinuric were linear in the range of 1.25-320 microg/L, 1.25-1280 microg/L and 1.25-1280 microg/L, respectivly. All with a low determination limits of 1.25 microg/L and a less than 9% within-day and inter-day RSD. The recovery rates reached 89% to 105%. CONCLUSION: The method is simple, rapid, sensitive, and suitable for the determination of nicacid and its metabolites in human plasma.

[Determination of lovastatin and its active metabolites in human plasma with high performance liquid chromatography-tandem mass spectrometry].

OBJECTIVE: To develop a sensitive LC-MS/MS method for analyzing lovastatin and its active metabolites lovastatin acid in human plasma. METHODS: Lovastatin and lovastatin acid were extracted from plasma by ethyl ether -dichloromethane (V/V, 1:1), with simvastatin serving as an internal standard. The analytes went through the column of Phenomenex Gemini C18 (50 x 3 mm, 3 microm) with mobile phase acetonitrile-water (85:15), and was analyzed by API3000 after protonated with ESI mode. The ion pairs being detected were 427.4-->325.4, 445.4-->343.4 and 436.4-->325.4, respectively. RESULTS: The established method was able to determine lovastatin in human plasma over the range of 0.03125-64 microg/L, with recovery rates ranging from 96% to 102%. The intra and inter day variances were below 9.3%. CONCLUSION: The LC-MS/MS method for analyzing lovastatin is validated and is suitable for clinical pharmacokinetic studies.