Cell-specific NFIA upregulation promotes epileptogenesis by TRPV4-mediated astrocyte reactivity.

BACKGROUND: The astrocytes in the central nervous system (CNS) exhibit morphological and functional diversity in brain region-specific pattern. Functional alterations of reactive astrocytes are commonly present in human temporal lobe epilepsy (TLE) cases, meanwhile the neuroinflammation mediated by reactive astrocytes may advance the development of hippocampal epilepsy in animal models. Nuclear factor I-A (NFIA) may regulate astrocyte diversity in the adult brain. However, whether NFIA endows the astrocytes with regional specificity to be involved in epileptogenesis remains elusive. METHODS: Here, we utilize an interference RNA targeting NFIA to explore the characteristics of NFIA expression and its role in astrocyte reactivity in a 4-aminopyridine (4-AP)-induced seizure model in vivo and in vitro. Combined with the employment of a HA-tagged plasmid overexpressing NFIA, we further investigate the precise mechanisms how NIFA facilitates epileptogenesis. RESULTS: 4-AP-induced NFIA upregulation in hippocampal region is astrocyte-specific, and primarily promotes detrimental actions of reactive astrocyte. In line with this phenomenon, both NFIA and vanilloid transient receptor potential 4 (TRPV4) are upregulated in hippocampal astrocytes in human samples from the TLE surgical patients and mouse samples with intraperitoneal 4-AP. NFIA directly regulates mouse astrocytic TRPV4 expression while the quantity and the functional activity of TRPV4 are required for 4-AP-induced astrocyte reactivity and release of proinflammatory cytokines in the charge of NFIA upregulation. NFIA deficiency efficiently inhibits 4-AP-induced TRPV4 upregulation, weakens astrocytic calcium activity and specific astrocyte reactivity, thereby mitigating aberrant neuronal discharges and neuronal damage, and suppressing epileptic seizure. CONCLUSIONS: Our results uncover the critical role of NFIA in astrocyte reactivity and illustrate how epileptogenic brain injury initiates cell-specific signaling pathway to dictate the astrocyte responses.

Degradation of Levofloxacin by a green zero-valent iron-loaded carbon composite activating peroxydisulfate system: Reactivity, products and mechanism.

In this study, a green zero-valent iron-loaded carbon composite (ZVI-SCG) was synthesized using coffee grounds and FeCl3 solution through two-steps method, and the synthesized ZVI-SCG was used in the activation of peroxydisulfate (PDS) to degrade Levofloxacin (LEX). Results revealed that ZVI-SCG exhibited a great potential for LEX removal by adsorption and catalytic degradation in the ZVI-SCG/PDS system, and 99% of LEX was removed in the ZVI-SCG/PDS system within 60 min. ZVI-SCG/PDS system showed a high reactivity toward LEX degradation under realistic environmental conditions. Also, the ZVI-SCG/PDS system could effectively degrade several quinolone antibiotics including gatifloxacin, ciprofloxacin and LEX in single and simultaneous removal modes. A potential reaction mechanism of LEX degradation by ZVI-SCG/PDS system was proposed, SO4•-, HO•, O2•- and 1O2 involved in radical and non-radical pathways took part in catalytic degradation of LEX by ZVI-SCG/PDS system, but HO• might be the main reactive species for LEX degradation. The possible degradation pathway of LEX was also proposed based on the identified ten intermediate products, LEX degradation was successfully achieved through decarboxylation, opening ring and hydroxylation processes. The potential toxicity of LEX and its oxidation products decreased significantly after treatment. This study provides a promising strategy of water treatment for the antibiotics-containing wastewater.

The potential mechanism of Neu5Gc inducing colorectal cancer based on network pharmacology and experimental validation.

Colorectal cancer has high morbidity and mortality worldwide, especially in western countries; the incidence of colorectal cancer has been high, which is closely related to the high intake of red meat; and the N-glycolylneuraminic acid (Neu5Gc) is responsible for red meat-induced colorectal cancer. A large number of previous studies have suggested that exogenous Neu5Gc-activated inflammation induced the occurrence of colorectal cancer. However, it has not been known whether the Neu5Gc has a direct inducing effect on colorectal cancer. In this study, we found that Neu5Gc promoted the proliferation of colorectal cancer cells and normal intestinal epithelial cells, and further screened out 98 Neu5Gc targets related to the occurrence and development of colorectal cancer by network pharmacology. Subsequently, GO and KEGG enrichment analyses of these targets revealed that mainly enriched in the PI3K-Akt signaling pathway. Then, we selected SRC, HRAS, CDK2, CCNA2, and AKT2 as core targets based on the phenomena of the previous experiments and the available literature reports, and then we used AutoDock for molecular docking with Neu5Gc; the results found that these five genes could bind to Neu5Gc stably. In vitro experiments showed that the mRNA levels of SRC, HRAS, AKT2, CDK2, and CCNA2 were upregulated and the protein levels of HRAS, AKT2, and CCNA2 were enhanced in FHC and SW620 cells after Neu5Gc (100 ng/mL) treatment. In conclusion, this study revealed that Neu5Gc probably acted as a carcinogen that stimulates the expression of proto-oncogene HRAS and the PI3K-Akt pathway and accelerated cell cycle progression. These findings revealed a novel mechanism that Neu5Gc promoted the occurrence and development of colorectal cancer.

A porous biochar supported nanoscale zero-valent iron material highly efficient for the simultaneous remediation of cadmium and lead contaminated soil.

Risk associated with heavy metals in soil has been received widespread attention. In this study, a porous biochar supported nanoscale zero-valent iron (BC-nZVI) was applied to immobilize cadmium (Cd) and lead (Pb) in clayey soil. Experiment results indicated that the immobilization of Cd or Pb by BC-nZVI process was better than that of BC or nZVI process, and about 80% of heavy metals immobilization was obtained in BC-nZVI process. Addition of BC-nZVI could increase soil pH and organic matter (SOM). Cd or Pb immobilization was inhibited with coexisting organic compound 2,4-dichlorophenol (2,4-DCP), but 2,4-DCP could be removed in a simultaneous manner with Cd or Pb immobilization at low concentration levels. Simultaneous immobilization of Cd and Pb was achieved in BC-nZVI process, and both Cd and Pb availability significantly decreased. Stable Cd species inculding Cd(OH)2, CdCO3 and CdO were formed, whereas stable Pb species such as PbCO3, PbO and Pb(OH)2 were produced with BC-nZVI treatment. Simultaneous immobilization mechanism of Cd and Pb in soil by BC-nZVI was thereby proposed. This study well demonstrates that BC-nZVI has been emerged as a potential technology for the remediation of multiple heavy metals in soil.

Access to acridones by tandem copper(I)-catalyzed electrophilic amination/Ag(I)-mediated oxidative annulation of anthranils with arylboronic acids.

An efficient and practical approach for the synthesis of medicinally important acridones was developed from anthranils and commercially available arylboronic acids by a tandem copper(I)-catalyzed electrophilic amination/Ag(I)-mediated oxidative annulation strategy. This new and straightforward protocol displayed a broad substrate scope (25 examples) and high functional group tolerance. What's more, a possible mechanistic proposal was also presented.

Simultaneous adsorption of Cr(VI) and phenol by biochar-based iron oxide composites in water: Performance, kinetics and mechanism.

The pollution of heavy metals and organic compounds has received increased attention in recent years. In the current study, a novel biochar-based iron oxide composite (FeYBC) was successfully synthesized using pomelo peel and ferric chloride solution through one-step process at moderate temperature. Results clearly demonstrate that FeYBC exhibited more efficient removal of Cr(VI) and/or phenol compared with the pristine biochar, and the maximum adsorption amounts of Cr(VI) and phenol by FeYBC could reach 24.37 and 39.32 mg g-1, respectively. A series of characterization data suggests that several iron oxides such as Fe2O3, Fe0, FeOOH and Fe3O4 were formed on the FeYBC surface as well as oxygen-containing groups. Thermodynamics study indicates that Cr(VI) and phenol adsorption by FeYBC were endothermic and exothermic processes, respectively. Langmuir adsorption isotherm and pseudo-second order models could better explain the Cr(VI) and phenol adsorption behaviors over FeYBC. The Cr(VI) adsorption might be primarily achieved through the ion exchange and surface complexation and reduction, whereas the π-π interaction and electron donor-acceptor complex mainly contributed to phenol adsorption. The findings indicate that the biochar-based iron oxide composites material was an efficient adsorbent for the remediation of industrial effluents containing Cr(VI) and phenol.

Ultrasound-assisted catalytic reduction of Cr(VI) by an acid mine drainage based nZVI coupling with FeS2 system from aqueous solutions: Performance and mechanism.

Nowadays, nanoscale zero valent iron (nZVI) has been extensively applied for the decontamination of various pollutants, but passivation of nZVI severely affects its reactivity in use. In this study, ultrasound (US)-assisted catalytic reduction of Cr(VI) by an acid mine drainage based nZVI (AMD-nZVI) coupling with FeS2 system was systematically examined. Results show that the presence of FeS2 and US induced a synergistic enhancement of Cr(VI) removal by AMD-nZVI. Nearly 98% of Cr(VI) removal was achieved by AMD-nZVI/FeS2/US process within 60 min under optimal reaction conditions. Several coexisting substances with lower concentration including Pb(II), Ni(II), bisphenol A (BPA) and 2,4-diclorophenol (2,4-DCP) could be effectively removed in simultaneous manner with Cr(VI) removal. The inhibitory order of water matrix species on Cr(VI) removal was NO3- > PO43- > HCO3- > Ca2+ > Mg2+ > Cl-, and a serious suppression effect was induced by humic acid (HA). Addition of ethylene diamine tetra-acetic acid (EDTA) and citric acid (CA) could enhance Cr(VI) removal rate. An enhanced reaction mechanism was proposed, which involved the regeneration of more Fe2+ and H+ by AMD-nZVI/FeS2/US process, leading to the reduction of Cr(VI) by AMD-nZVI and FeS2 into Cr(III) species inculding Cr2O3 and Cr(OH)3. This study well demonstrates that AMD-nZVI/FeS2/US process is considered as a potential candidate for the remediation of Cr(VI) in real wasterwater.

Efficacy of indoor air purification in the treatment of Artemisia pollen-allergic rhinitis: A randomised, double-blind, clinical controlled trial.

OBJECTIVES: To evaluate the clinical efficacy of a high-efficiency air purifier in patients with allergic rhinitis. DESIGN: We conducted a randomised, double-blind, clinical controlled trial with active and inactive versions of an air purifier. Our study included patients with allergic rhinitis who were sensitive to Artemisia pollen and treatment of the indoor environment using air filtration at night. We evaluated the clinical efficacy of indoor air filtration during the Artemisia pollen scattering season in Yulin City in Shanxi Province, China. SETTING: The First Hospital of Yulin (Yulin City, Shanxi Province, China). PARTICIPANTS: A total of 90 patients with allergic rhinitis who were sensitive to allergens of Artemisia pollen were randomly assigned to one of two groups in equal numbers. MAIN OUTCOME MEASURES: The primary outcome measure was the difference in visual analogue scale scores from baseline. Secondary outcomes were changes from baseline in nasal symptoms, allergy symptom scores, responses to the Rhinoconjunctivitis Quality of Life Questionnaire, Epworth Sleepiness Scale scores and tolerability scores for the air purifier. RESULTS: Based on the allergy symptom score, we found significant differences in rhinitis symptoms between the groups who used the active versus the inactive air purifier. CONCLUSIONS: The results of our investigation demonstrated the health benefits of particle filtration.