Carbon footprint of farming practices in farmland ecosystems on the North and Northeast China plains.

Fast development of farming practices in China is projected to result in additional carbon emissions and thus affect farmland ecosystems' environmental performance. Based on 454 farm surveys on the North and Northeast China Plain, the carbon footprint (CF) of two farmland ecosystems (irrigated system for wheat and maize on the North China Plain and rainfed system for maize on the Northeast Plain) were assessed and emission reduction pathways explored by quantifying greenhouse gas emissions of agricultural inputs and farm practices during the entire crop growing seasons with an agricultural footprint model. The results demonstrated that the GHG emissions from wheat and maize rotation in the irrigated system were 7.63 t CO2 eq ha-1 and 3.17 t CO2 eq ha-1 for single season maize in the rainfed system. While energy consumption accounted for 12.5%-21.3% of the carbon footprint in both systems, the group assessment found that the largest difference in GHG emissions between the high and low emission groups came from mechanical energy consumption. Approximately 50.6% and 39.2% of the mechanical carbon footprint of wheat and maize, respectively, were caused by irrigation practices in the irrigated system. Regarding the rainfed system, where 46.6% of mechanical carbon emissions were generated by maize tillage operations. In addition, scenario analysis indicated that the mechanical carbon footprint could be reduced to 56 kg CO2 eq t-1 for NCP-wheat and 26 kg CO2 eq t-1 for NCP-maize, respectively, by optimizing yields and irrigation practices in irrigated systems and that the mechanical carbon footprint of NEP-maize could be reduced to 25 kg CO2 eq t-1 by optimizing yields and tillage practices in rainfed systems. Therefore, improvement in mechanization in irrigation and tillage practices can contribute to reduce GHG emissions in China. Water-saving irrigation technology is recommended in irrigated area and conservation tillage is recommended in rainfed agricultural area to reduce carbon footprints.

A Combined Virtual Electrode-Based ESA and CNN Method for MI-EEG Signal Feature Extraction and Classification.

A Brain-Computer Interface (BCI) is a medium for communication between the human brain and computers, which does not rely on other human neural tissues, but only decodes Electroencephalography (EEG) signals and converts them into commands to control external devices. Motor Imagery (MI) is an important BCI paradigm that generates a spontaneous EEG signal without external stimulation by imagining limb movements to strengthen the brain's compensatory function, and it has a promising future in the field of computer-aided diagnosis and rehabilitation technology for brain diseases. However, there are a series of technical difficulties in the research of motor imagery-based brain-computer interface (MI-BCI) systems, such as: large individual differences in subjects and poor performance of the cross-subject classification model; a low signal-to-noise ratio of EEG signals and poor classification accuracy; and the poor online performance of the MI-BCI system. To address the above problems, this paper proposed a combined virtual electrode-based EEG Source Analysis (ESA) and Convolutional Neural Network (CNN) method for MI-EEG signal feature extraction and classification. The outcomes reveal that the online MI-BCI system developed based on this method can improve the decoding ability of multi-task MI-EEG after training, it can learn generalized features from multiple subjects in cross-subject experiments and has some adaptability to the individual differences of new subjects, and it can decode the EEG intent online and realize the brain control function of the intelligent cart, which provides a new idea for the research of an online MI-BCI system.

[Research Progress of microRNA-7/124/155 in Parkinson's Disease].

Parkinson's disease(PD)is the second most common neurodegenerative disease after Alzheimer's disease,with high morbidity and high disability rate.Since the early symptoms of PD are not typical and often similar to those of normal aging or other diseases.It is easy to missed diagnosis and misdiagnosis,which seriously affects the diagnosis and treatment of this disease and aggravetes the burden on the patients' life.MicroRNAs(miRNA)are a class of endogenous non-coding RNAs that are involved in post-transcriptional regulation by binding to target messenger RNAs(mRNA).They are highly conserved,short,easy to obtain,and can stably exist in peripheral body fluids.They have been used as biomarkers for a variety of diseases.Recent studies have demonstrated that miRNA play an important role in the development of PD.This paper reviews the recent research progress of miR-7/124/155,three mature miRNA in PD,aiming to provide reference for clarifying the pathogenesis and guiding the diagnosis and treatment of PD.

UVA-LED-Assisted Activation of the Ferrate(VI) Process for Enhanced Micropollutant Degradation: Important Role of Ferrate(IV) and Ferrate(V).

This paper investigated ultraviolet A light-emitting diode (UVA-LED) irradiation to activate Fe(VI) for the degradation of micropollutants (e.g., sulfamethoxazole (SMX), enrofloxacin, and trimethoprim). UVA-LED/Fe(VI) could significantly promote the degradation of micropollutants, with rates that were 2.6-7.2-fold faster than for Fe(VI) alone. Comparatively, UVA-LED alone hardly degraded selected micropollutants. The degradation performance was further evaluated in SMX degradation via different wavelengths (365-405 nm), light intensity, and pH. Increased wavelengths led to linearly decreased SMX degradation rates because Fe(VI) has a lower molar absorption coefficient at higher wavelengths. Higher light intensity caused faster SMX degradation, owing to the enhanced level of reactive species by stronger photolysis of Fe(VI). Significantly, SMX degradation was gradually suppressed from pH 7.0 to 9.0 due to the changing speciation of Fe(VI). Scavenging and probing experiments for identifying oxidative species indicated that high-valent iron species (Fe(V)/Fe(IV)) were responsible for the enhanced degradation. A kinetic model involving target compound (TC) degradation by Fe(VI), Fe(V), and Fe(IV) was employed to fit the TC degradation kinetics by UVA-LED/Fe(VI). The fitted results revealed that Fe(IV) and Fe(V) primarily contributed to TC degradation in this system. In addition, transformation products of SMX degradation by Fe(VI) and UVA-LED/Fe(VI) were identified and the possible pathways included hydroxylation, self-coupling, bond cleavage, and oxidation reactions. Removal of SMX in real water also showed remarkable promotion by UVA-LED/Fe(VI). Overall, these findings could shed light on the understanding and application of UVA-LED/Fe(VI) for eliminating micropollutants in water treatments.

Enhanced Permanganate Activation under UVA-LED Irradiation: Unraveled Mechanism Involving Manganese Species and Hydroxyl Radical.

Permanganate [Mn(VII)] has gained broad attention in water treatment. However, its limited reactivity toward some refractory micropollutants hinders its application for micropollutant degradation. Herein, we introduced UVA-LED photolysis of Mn(VII) (UVA-LED/Mn(VII)) to degrade micropollutants (diclofenac (DCF), 4-chlorophenol (4-CP), atrazine, and nitrobenzene) by selecting DCF and 4-CP as target micropollutants. The effects of operating conditions (e.g., light intensity, radiation wavelengths, pH, and water constituents) on DCF and 4-CP degradation as well as the underlying mechanisms were systematically studied. The degradation rates of DCF and 4-CP linearly decreased with increasing radiation wavelengths (from 365 to 405 nm), likely due to the decreased molar absorption coefficients and quantum yields of Mn(VII). Reactive manganese species (RMnS), including Mn(V), Mn(III), and HO•, were generated in the UVA-LED/Mn(VII) process. Mn(V) and HO• were responsible for DCF degradation, while Mn(III), HO•, and likely Mn(V) accounted for 4-CP degradation. Competitive kinetic results revealed that contributions of RMnS and HO• decreased with increasing radiation wavelengths, wherein RMnS played the dominant role. Increasing pH displayed opposite effects on DCF and 4-CP degradation with higher degradation efficiency obtained at acidic pH for the former one but alkaline pH for the latter one. The presence of water background ions (e.g., Cl-, HCO3-, and Ca2+) barely influenced DCF and 4-CP degradation. Finally, in comparison with Mn(VII) alone, enhanced degradation of DCF and 4-CP by UVA-LED/Mn(VII) was observed in real waters. This work advances the understanding of the photochemistry of manganese species in micropollutant degradation and facilitates Mn(VII) oxidation in practical application.

MicroRNAs 29b and 181a down-regulate the expression of the norepinephrine transporter and glucocorticoid receptors in PC12 cells.

MicroRNAs are short non-coding RNAs that provide global regulation of gene expression at the post-transcriptional level. Such regulation has been found to play a role in stress-induced epigenetic responses in the brain. The norepinephrine transporter (NET) and glucocorticoid receptors are closely related to the homeostatic integration and regulation after stress. Our previous studies demonstrated that NET mRNA and protein levels in rats are regulated by chronic stress and by administration of corticosterone, which is mediated through glucocorticoid receptors. Whether miRNAs are intermediaries in the regulation of these proteins remains to be elucidated. This study was undertaken to determine possible regulatory effects of miRNAs on the expression of NET and glucocorticoid receptors in the noradrenergic neuronal cell line. Using computational target prediction, we identified several candidate miRNAs potentially targeting NET and glucocorticoid receptors. Western blot results showed that over-expression of miR-181a and miR-29b significantly repressed protein levels of NET, which is accompanied by a reduced [3 H] norepinephrine uptake, and glucocorticoid receptors in PC12 cells. Luciferase reporter assays verified that both miR-181a and miR-29b bind the 3'UTR of mRNA of NET and glucocorticoid receptors. Furthermore, exposure of PC12 cells to corticosterone markedly reduced the endogenous levels of miR-29b, which was not reversed by the application of glucocorticoid receptor antagonist mifepristone. These observations indicate that miR-181a and miR-29b can function as the negative regulators of NET and glucocorticoid receptor translation in vitro. This regulatory effect may be related to stress-induced up-regulation of the noradrenergic phenotype, a phenomenon observed in stress models and depressive patients. This study demonstrated that miR-29b and miR-181a, two short non-coding RNAs that provide global regulation of gene expression, markedly repressed protein levels of norepinephrine (NE) transporter and glucocorticoid receptor (GR), as well as NE uptake by binding the 3'UTR of their mRNAs in PC12 cells. Also, exposure of cells to corticosterone significantly reduced miR-29b levels through a GR-independent way.

Corticotropin releasing factor up-regulates the expression and function of norepinephrine transporter in SK-N-BE (2) M17 cells.

Corticotropin releasing factor (CRF) has been implicated to act as a neurotransmitter or modulator in central nervous activation during stress. In this study, we examined the regulatory effect of CRF on the expression and function of the norepinephrine transporter (NET) in vitro. SK-N-BE (2) M17 cells were exposed to different concentrations of CRF for different periods. Results showed that exposure of cells to CRF significantly increased mRNA and protein levels of NET in a concentration- and time-dependent manner. The CRF-induced increase in NET expression was mimicked by agonists of either CRF receptor 1 or 2. Furthermore, similar CRF treatments induced a parallel increase in the uptake of [(3) H] norepinephrine. Both increased expression and function of NET caused by CRF were abolished by simultaneous administration of CRF receptor antagonists, indicating a mediation by CRF receptors. However, there was no additive effect for the combination of both receptor antagonists. Chromatin immunoprecipitation assays confirm an increased acetylation of histone H3 on the NET promoter following treatment with CRF. Taken together, this study demonstrates that CRF up-regulates the expression and function of NET in vitro. This regulation is mediated through CRF receptors and an epigenetic mechanism related to histone acetylation may be involved. This CRF-induced regulation on NET expression and function may play a role in development of stress-related depression and anxiety. This study demonstrated that corticotropin release factor (CRF) up-regulated the expression and function of norepinephrine transporter (NET) in a concentration- and time-dependent manner, through activation of CRF receptors and possible histone acetylation in NET promoter. The results indicate that their interaction may play an important role in stress-related physiological and pathological status.

Corticosterone administration up-regulated expression of norepinephrine transporter and dopamine ß-hydroxylase in rat locus coeruleus and its terminal regions.

Stress has been reported to activate the locus coeruleus (LC)-noradrenergic system. In this study, corticosterone (CORT) was orally administrated to rats for 21 days to mimic stress status. In situ hybridization measurements showed that CORT ingestion significantly increased mRNA levels of norepinephrine transporter (NET) and dopamine ß-hydroxylase (DBH) in the LC region. Immunofluorescence staining and western blotting revealed that CORT treatment also increased protein levels of NET and DBH in the LC, as well as NET protein levels in the hippocampus, the frontal cortex and the amygdala. However, CORT-induced increase in DBH protein levels only appeared in the hippocampus and the amygdala. Elevated NET and DBH expression in most of these areas (except for NET protein levels in the LC) was abolished by simultaneous treatment with combination of corticosteroid receptor antagonist mifepristone and spironolactone (s.c. for 21 days). Also, treatment with mifepristone alone prevented CORT-induced increases of NET expression and DBH protein levels in the LC. In addition, behavioral tasks showed that CORT ingestion facilitated escape in avoidance trials using an elevated T-maze, but interestingly, there was no significant effect on the escape trial. Corticosteroid receptor antagonists failed to counteract this response in CORT-treated rats. In the open-field task, CORT treatment resulted in less activity in a defined central zone compared to controls and corticosteroid receptor antagonist treatment alleviated this increase. In conclusion, this study demonstrates that chronic exposure to CORT results in a phenotype that mimics stress-induced alteration of noradrenergic phenotypes, but the effects on behavior are task dependent. As the sucrose consumption test strongly suggests CORT ingestion-induced depression-like behavior, further elucidation of underlying mechanisms may improve our understanding of the correlation between stress and the development of depression.

Effects of chronic social defeat on expression of dopamine ß-hydroxylase in rat brains.

It is documented that stress activates the locus coeruleus-norepinephrine system. However, there are far few reports regarding effects of stress on the expression of dopamine ß-hydroxylase, a hallmark enzyme of the noradrenergic neuron. In the present study, adult Fischer 344 rats were subjected to chronic social defeat for 4 weeks. Dopamine ß-hydroxylase expressional levels in the locus coeruleus and its terminal regions were measured by in situ hybridization and western blotting. The results showed that immediately following chronic social defeat there are significantly increased mRNA and protein levels of dopamine ß-hydroxylase in the locus coeruleus, and dopamine ß-hydroxylase protein levels in the hippocampus, frontal cortex and amygdala, compared with those in the control. This chronic social defeat-induced upregulation of dopamine ß-hydroxylase was completely abolished by adrenalectomy, and/or by treatment with corticosteroid receptor antagonists, mifepristone and spironolactone, either alone or in combination. Furthermore, treatment with desipramine, an antidepressant with specific inhibitory effects on norepinephrine transport, prevented an increased dopamine ß-hydroxylase expression by chronic social defeat in the locus coeruleus and its main terminal regions such as the hippocampus, frontal cortex and amygdala. However, treatment with fluoxetine, an antidepressant with specific inhibition for serotonin transport, only selectively blocked increased dopamine ß-hydroxylase protein levels in the hippocampus caused by CSD. The present findings indicate that chronic social defeat activates the locus coeruleus-norepinephrine system by upregulating the expression of dopamine ß-hydroxylase, which may increase norepinephrine synthesis. This chronic social defeat induced upregulation of DBH expression was mediated through corticosterone and corticosteroid receptors, with possible interference from antidepressants.

Upregulated DNA Damage-Linked Biomarkers in Parkinson's Disease Model Mice.

SUMMARY STATEMENT: The present study examined expression of DNA damage markers in VMAT2 Lo PD model mice. The results demonstrate there is a significant increase in these DNA damage markers mostly in the brain regions of 18- and 23-month-old model mice, indicating oxidative stress-induced DNA lesion is an important pathologic feature of this mouse model.

Photolysis of chlorite by solar light: An overlooked mitigation pathway for chlorite and micropollutants.

Chlorite (ClO2-) is an undesirable toxic byproduct commonly produced in the chlorine dioxide and ultraviolet/chlorine dioxide oxidation processes. Various methods have been developed to remove ClO2- but require additional chemicals or energy input. In this study, an overlooked mitigation pathway of ClO2- by solar light photolysis with a bonus for simultaneous removal of micropollutant co-present was reported. ClO2- could be efficiently decomposed to chloride (Cl-) and chlorate by simulated solar light (SSL) at water-relevant pHs with Cl- yield up to 65% at neutral pH. Multiple reactive species including hydroxyl radical (•OH), ozone (O3), chloride radical (Cl•), and chlorine oxide radical (ClO•) were generated in the SSL/ClO2- system with the steady-state concentrations following the order of O3 (≈ 0.8 µΜ) > ClO• (≈ 4.4 × 10-6 µΜ)> •OH (≈ 1.1 × 10-7 µΜ)> Cl• (≈ 6.8 × 10-8 µΜ) at neutral pH under investigated condition. Bezafibrate (BZF) as well as the selected six other micropollutants was efficiently degraded by the SSL/ClO2- system with pseudofirst-order rate constants ranging from 0.057 to 0.21 min-1 at pH 7.0, while most of them were negligibly degraded by SSL or ClO2- treatment alone. Kinetic modeling of BZF degradation by SSL/ClO2- at pHs 6.0 - 8.0 suggested that •OH contributed the most, followed by Cl•, O3, and ClO•. The presence of water background components (i.e., humic acid, bicarbonate, and chloride) exhibited negative effects on BZF degradation by the SSL/ClO2- system, mainly due to their competitive scavenging of reactive species therein. The mitigation of ClO2- and BZF under photolysis by natural solar light or in realistic waters was also confirmed. This study discovered an overlooked natural mitigation pathway for ClO2- and micropollutants, which has significant implications for understanding their fate in natural environments.

Chronic social defeat up-regulates expression of the serotonin transporter in rat dorsal raphe nucleus and projection regions in a glucocorticoid-dependent manner.

Chronic stress and dysfunction of the serotonergic system in the brain have been considered two of the major risks for development of depression. In this study, adult Fischer 344 rats were subjected to a regimen of chronic social defeat (CSD). To mimic stressful conditions, some rats were not exposed to CSD, but instead treated with corticosterone (CORT) in oral solution while maintained in their home cage. Protein levels of the serotonin transporter (SERT) in the dorsal raphe nucleus (DRN), hippocampus, frontal cortex, and amygdala were examined by Western blotting or immunofluorescence staining. The results showed that CSD up-regulated SERT protein levels in the DRN, hippocampus, frontal cortex, and amygdala regions. This up-regulation was abolished or prevented by adrenalectomy, or treatment with antagonists of corticosteroid receptors mifepristone and spironolactone, alone or in combination. Similarly, up-regulated SERT protein levels in these brain regions were also observed in rats treated with oral CORT ingestion, which was analogously prevented by treatment with mifepristone and spironolactone. Furthermore, both CSD- and CORT-induced up-regulation of SERT protein levels in the DRN and three brain regions were attenuated by simultaneous treatment with fluoxetine, an antidepressant that specifically inhibits serotonin reuptake. The results indicate that up-regulation in SERT protein levels in the DRN and forebrain limbic structures caused by CSD regimen was mainly motivated by CORT through corticosteroid receptors. The present findings demonstrate that chronic stress is closely correlated with the serotonergic system by acting on the regulation of the SERT expression in the DRN and its projection regions, which may contribute to the development of depression.

Low gene expression of bone morphogenetic protein 7 in brainstem astrocytes in major depression.

The noradrenergic locus coeruleus (LC) is the principal source of brain norepinephrine, a neurotransmitter thought to play a major role in the pathology of major depressive disorder (MDD) and in the therapeutic action of many antidepressant drugs. The goal of this study was to identify potential mediators of brain noradrenergic dysfunction in MDD. Bone morphogenetic protein 7 (BMP7), a member of the transforming growth factor-ß superfamily, is a critical mediator of noradrenergic neuron differentiation during development and has neurotrophic and neuroprotective effects on mature catecholaminergic neurons. Real-time PCR of reversed transcribed RNA isolated from homogenates of LC tissue from 12 matched pairs of MDD subjects and psychiatrically normal control subjects revealed low levels of BMP7 gene expression in MDD. No differences in gene expression levels of other members of the BMP family were observed in the LC, and BMP7 gene expression was normal in the prefrontal cortex and amygdala in MDD subjects. Laser capture microdissection of noradrenergic neurons, astrocytes, and oligodendrocytes from the LC revealed that BMP7 gene expression was highest in LC astrocytes relative to the other cell types, and that the MDD-associated reduction in BMP7 gene expression was limited to astrocytes. Rats exposed to chronic social defeat exhibited a similar reduction in BMP7 gene expression in the LC. BMP7 has unique developmental and trophic actions on catecholamine neurons and these findings suggest that reduced astrocyte support for pontine LC neurons may contribute to pathology of brain noradrenergic neurons in MDD.

Enhanced removal of organoarsenic by chlorination: Kinetics, effect of humic acid, and adsorbable chlorinated organoarsenic.

In this study, the effective removal of organoarsenic by the combined process of "chlorination + Fe(II)" was achieved. Chlorine could effectively degrade roxarsone (ROX) over pH from 5 to 10. The fitting results of acid-base protonation model proved that the degradation of ROX was mainly attributed to the reaction of HOCl and deprotonated ROX. The transformation of arsenic species conformed to the fitting results of two-channel kinetic model, in which 32.4% of ROX was oxidized to As(V) via electron transfer pathway (ii) and the rest was converted into monochloro-ROX via electrophilic substitution pathway (i). Humic acid inhibited the degradation of ROX due to the competitive consumption of chlorine and the restraint on the pathway ii. Subsequently, an enhanced removal of total arsenic achieved after chlorination, due to that the generating As(V) and monochloro-ROX were easier adsorbed compared with ROX, over 97.8% of total arsenic was removed by ferric (oxyhydr)oxides which in-situ formed from the oxidation of Fe(II). Additionally, toxicity studies indicated that the acute toxicity was significantly eliminated by adding Fe(II) after chlorination, likely due to the removal of As(V) and chlorinated products. Furthermore, organoarsenic was also effectively removed by the combined process of "chlorination + Fe(II)" in real water.

Dexamethasone-induced up-regulation of the human norepinephrine transporter involves the glucocorticoid receptor and increased binding of C/EBP-ß to the proximal promoter of norepinephrine transporter.

Previously, we have found glucocorticoids up-regulate norepinephrine (NE) transporter (NET) expression in vitro. However, the underlying transcriptional mechanism is poorly understood. In this study, the role of glucocorticoids on the transcriptional regulation of NET was investigated. Exposure of neuroblastoma SK-N-BE(2)M17 cells to dexamethasone (Dex) significantly increased NET mRNA and protein levels in a time- and dose-dependent manner. This effect was attenuated by glucocorticoid receptor (GR) antagonist mifepristone, suggesting that up-regulation of NET by Dex was mediated by the GR. In reporter gene assays, exposure of cells to Dex resulted in dose-dependent increases of luciferase activity that were also prevented by mifepristone. Serial deletions of the NET promoter delineated Dex-responsiveness to a -301 to -148 bp region containing a CCAAT/enhancer binding protein-ß (C/EBP-ß) response element. Co-immunoprecipitation experiments demonstrated that Dex treatment caused the interaction of the GR with C/EBP-ß. Chromatin immunoprecipitation (ChIP) assay revealed that Dex exposure resulted in binding of both GR and C/EBP-ß to the NET promoter. Further experiments showed that mutation of the C/EBP-ß response element abrogated C/EBP-ß- and GR-mediated transactivation of NET. These findings demonstrate that Dex-induced increase in NET expression is mediated by the GR via a non-conventional transcriptional mechanism involving interaction of C/EBP-ß with a C/EBP-ß response element.

Insight into enhanced activation of permanganate under simulated solar irradiation: Rapid formation of manganese species.

Herein, permanganate [Mn(VII)] was activated by simulated solar (SS) (SS/Mn(VII)), resulting in rapid degradation of micropollutants in several minutes, with rates of target micropollutants outnumbered those in the Mn(VII) alone and SS. To explore the mechanism in this process, 4-cholorphenol (4-CP), p-hydroxybenzoic acid (p-HBA), and enrofloxacin (ENR) were selected as model compounds. Lines of evidence indicated that reactive manganese species (RMnS) (i.e., Mn(III) and Mn(V)) rather than radicals from Mn(VII) photolysis participated in the conversion of model compounds. Interestingly, roles of RMnS differed among three model compounds, suggesting their selectivity toward micropollutants. Increasing Mn(VII) dosage proved greater micropollutant degradation, while impacts of pH on SS/Mn(VII) performance varied among model compounds. P-HBA and ENR showed the lowest degradation efficiency at alkaline, whereas 4-CP demonstrated the best performance at alkaline, indicating the reactivity of RMnS varied toward micropollutants at different pH values. The quantum yield of Mn(VII) was 8.36 ± 0.03 X 10-6 mol Einstein-1 at pH 7.0. Effects of common co-existing constituents (Cl-, HCO3-, and humic acid (HA)) on micropollutant degradation by SS/Mn(VII) were examined. Specifically, HCO3- positively influenced the 4-CP and p-HBA degradation, whereas ENR was not affected, likely owing to the selectivity of RMnS-HCO3- complexes. HA was conducive to degrade p-HBA due to the production of RMnS-HA complexes, but unfavorable for ENR and 4-CP degradation because of the competitive light absorption and Mn(VII). Furthermore, a number of degradation products of 4-CP, p-HBA, and ENR were identified and possible pathways were proposed accordingly. The effectiveness of this process for micropollutant degradation in real waters, natural sunlight, ultraviolet and visible light via cut-off filtering SS emission was confirmed. This work revealed a great potential of applying SS/Mn(VII) for the marked degradation of micropollutants and facilitated the understandings of Mn(III)/Mn(V) behaviors.

Effects of Manipulation of Noradrenergic Activities on the Expression of Dopaminergic Phenotypes in Aged Rat Brains.

This study investigated the effects of the pharmacological manipulation of noradrenergic activities on dopaminergic phenotypes in aged rats. Results showed that the administration of L-threo-3,4-dihydroxyphenylserine (L-DOPS) for 21 days significantly increased the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the striatum and substantia nigra (SN) of 23-month-old rats. Furthermore, this treatment significantly increased norepinephrine/DA concentrations in the striatum and caused a deficit of sensorimotor gating as measured by prepulse inhibition (PPI). Next, old rats were injected with the α2-adrenoceptor antagonist 2-methoxy idazoxan or ß2-adrenoceptor agonist salmeterol for 21 days. Both drugs produced similar changes of TH and DAT in the striatum and SN. Moreover, treatments with L-DOPS, 2-methoxy idazoxan, or salmeterol significantly increased the protein levels of phosphorylated Akt in rat striatum and SN. However, although a combination of 2-methoxy idazoxan and salmeterol resulted in a deficit of PPI in these rats, the administration of 2-methoxy idazoxan alone showed an opposite behavioral change. The in vitro experiments revealed that treatments with norepinephrine markedly increased mRNAs and proteins of ATF2 and CBP/p300 and reduced mRNA and proteins of HDAC2 and HDAC5 in MN9D cells. A ChIP assay showed that norepinephrine significantly increased CBP/p300 binding or reduced HDAC2 and HDAC5 binding on the TH promoter. The present results indicate that facilitating noradrenergic activity in the brain can improve the functions of dopaminergic neurons in aged animals. While this improvement may have biochemically therapeutic indication for the status involving the degeneration of dopaminergic neurons, it may not definitely include behavioral improvements, as indicated by using 2-methoxy idazoxan only.

Restoration of Noradrenergic Function in Parkinson's Disease Model Mice.

Dysfunction of the central noradrenergic and dopaminergic systems is the primary neurobiological characteristic of Parkinson's disease (PD). Importantly, neuronal loss in the locus coeruleus (LC) that occurs in early stages of PD may accelerate progressive loss of dopaminergic neurons. Therefore, restoring the activity and function of the deficient noradrenergic system may be an important therapeutic strategy for early PD. In the present study, the lentiviral constructions of transcription factors Phox2a/2b, Hand2 and Gata3, either alone or in combination, were microinjected into the LC region of the PD model VMAT2 Lo mice at 12 and 18 month age. Biochemical analysis showed that microinjection of lentiviral expression cassettes into the LC significantly increased mRNA levels of Phox2a, and Phox2b, which were accompanied by parallel increases of mRNA and proteins of dopamine ß-hydroxylase (DBH) and tyrosine hydroxylase (TH) in the LC. Furthermore, there was considerable enhancement of DBH protein levels in the frontal cortex and hippocampus, as well as enhanced TH protein levels in the striatum and substantia nigra. Moreover, these manipulations profoundly increased norepinephrine and dopamine concentrations in the striatum, which was followed by a remarkable improvement of the spatial memory and locomotor behavior. These results reveal that over-expression of these transcription factors in the LC improves noradrenergic and dopaminergic activities and functions in this rodent model of PD. It provides the necessary groundwork for the development of gene therapies of PD, and expands our understanding of the link between the LC-norepinephrine and dopamine systems during the progression of PD.

Corticosterone up-regulates expression and function of norepinephrine transporter in SK-N-BE(2)C cells.

Glucocorticoids affect cellular and molecular events in brains by modulating the expression of many genes during stress. In the present study, we examined the regulatory effect of corticosterone on the expression and function of the norepinephrine transporter (NET) in vitro. The results show that exposure of SK-N-BE(2)C cells to corticosterone for 14 days significantly increased mRNA (up to 43%) and protein (up to 71%) levels of NET in the concentration-dependent manner. Longer exposure (21 days) resulted in greater increases in the levels of mRNAs (up to about 160%) and proteins (up to about 250%) of the NET. The up-regulatory effect of corticosterone on NET expression lasted a persistent period after cessation of exposure. Associated with the corticosterone-induced enhancement in NET expression, there was a parallel increase in the uptake of [(3)H]norepinephrine by SK-N-BE(2)C cells. Increased NET expression and function were abolished after exposure of cells to corticosterone in combination with mifepristone or spironolactone, two specific antagonists of corticosteroid receptors. This is consistent with the hypothesis that corticosterone-induced NET up-regulation is mediated by corticosteroid receptors. Nevertheless, there was no synergistic effect for a combination of both corticosteroid receptor antagonists. A similar up-regulation of NET protein levels was also observed after exposing PC12 cells to corticosterone. The present findings demonstrate that corticosterone up-regulates the expression and function of NET in vitro, indicating the action of corticosterone on the noradrenergic phenotype may play an important role in the correlation between stress and the development of depression.

Transcription Factors Phox2a/2b Upregulate Expression of Noradrenergic and Dopaminergic Phenotypes in Aged Rat Brains.

The present study investigated the effects of forced overexpression of Phox2a/2b, two transcription factors, in the locus coeruleus (LC) of aged rats on noradrenergic and dopaminergic phenotypes in brains. Results showed that a significant increase in Phox2a/2b mRNA levels in the LC region was paralleled by marked enhancement in expression of DBH and TH per se. Furthermore, similar increases in TH protein levels were observed in the substantial nigra and striatum, as well as in the hippocampus and frontal cortex. Overexpression of Phox2 genes also significantly increased BrdU-positive cells in the hippocampal dentate gyrus and NE levels in the striatum. Moreover, this manipulation significantly improved the cognition behavior. The in vitro experiments revealed that norepinephrine treatments may increase the transcription of TH gene through the epigenetic action on the TH promoter. The results indicate that Phox2 genes may play an important role in improving the function of the noradrenergic and dopaminergic neurons in aged animals, and regulation of Phox2 gene expression may have therapeutic utility in aging or disorders involving degeneration of noradrenergic neurons.