HuB and HuD repress telomerase activity by dissociating HuR from TERC.

The ubiquitous RNA-binding protein HuR (ELAVL1) promotes telomerase activity by associating with the telomerase noncoding RNA TERC. However, the role of the neural-specific members HuB, HuC, and HuD (ELAVL2-4) in telomerase activity is unknown. Here, we report that HuB and HuD, but not HuC, repress telomerase activity in human neuroblastoma cells. By associating with AU-rich sequences in TERC, HuB and HuD repressed the assembly of the TERT-TERC core complex. Furthermore, HuB and HuD competed with HuR for binding to TERC and antagonized the function of HuR that was previously shown to enhance telomerase activity to promote cell growth. Our findings reveal a novel mechanism controlling telomerase activity in human neuroblastoma cells that involves a competition between HuR and the related, neural-specific proteins HuB and HuD.

Connexin 43 gap junction-mediated astrocytic network reconstruction attenuates isoflurane-induced cognitive dysfunction in mice.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication following anesthesia and surgery. General anesthetic isoflurane has potential neurotoxicity and induces cognitive impairments, but the exact mechanism remains unclear. Astrocytes form interconnected networks in the adult brain through gap junctions (GJs), which primarily comprise connexin 43 (Cx43), and play important roles in brain homeostasis and functions such as memory. However, the role of the GJ-Cx43-mediated astrocytic network in isoflurane-induced cognitive dysfunction has not been defined. METHODS: 4-month-old male C57BL/6 mice were exposure to long-term isoflurane to induce cognitive impairment. To simulate an in vitro isoflurane-induced cognitive dysfunction-like condition, primary mouse astrocytes were subjected to long-term isoflurane exposure. Cognitive function was assessed by Y-maze and fear conditioning tests. Western blot was used to determine the expression levels of different functional configurations of Cx43. The morphology of the GJs-Cx43 was evaluated by immunofluorescence staining. Levels of IL-1ß and IL-6 were examined by ELISA. The ability of GJs-Cx43-mediated intercellular communication was examined by lucifer yellow dye transfer assay. Ethidium bromide uptake assays were used to measure the activity of Cx43 hemichannels. The ultrastructural morphology of astrocyte gap junctions and tripartite synapse were observed by transmission electron microscopy. RESULTS: After long-term isoflurane anesthesia, the GJs formed by Cx43 in the mouse hippocampus and primary mouse astrocytes were significantly reduced, GJs function was impaired, hemichannel activity was enhanced, the levels of IL-1ß and IL-6 were increased, and mice showed significant cognitive impairment. After treatment with the novel GJ-Cx43 enhancer ZP1609, GJ-Cx43-mediated astrocytic network function was enhanced, neuroinflammation was alleviated, and ameliorated cognition dysfunction induced by long-term isoflurane exposure. However, ZP1609 enhances the astrocytic network by promoting Cx43 to form GJs without affecting hemichannel activity. Additionally, our data showed that long-term isoflurane exposure does not alter the structure of tripartite synapse. CONCLUSION: Our results reveal a novel mechanism of the GJ-Cx43-mediated astrocytic network involved in isoflurane-induced neuroinflammation and cognitive impairments, which provides new mechanistic insight into the pathogenesis of POCD and identifies potential targets for its treatment.

The role of 5-HT7R in the memory impairment of mice induced by long-term isoflurane anesthesia.

General anesthesia is widely utilized in the clinic for surgical and diagnostic procedures. However, growing evidence suggests that anesthetic exposure may affect cognitive function negatively. Unfortunately, little is known about the underlying mechanisms and efficient prevention and therapeutic strategies for the anesthesia-induced cognitive dysfunction. 5-HT7R, a serotonin receptor family member, is functionally associated with learning and memory. It has recently become a potential therapeutic target in various neurological diseases as its ligands have a wide range of neuropharmacological effects. However, it remains unknown the role of 5-HT7R in the long-term isoflurane anesthesia-induced memory impairment and whether prior activation or blockade of 5-HT7R before anesthesia has modulating effects on this memory impairment. In this study, 5-HT7R selective agonist LP-211 and 5-HT7R selective antagonist SB-269970 were pretreated intraperitoneally to mice before anesthesia; their effects on the cognitive performance of mice were assessed using fear conditioning test and novel object recognition test. Furthermore, the transcriptional level of 5-HT7R in the hippocampus was detected using qRT-PCR, and proteomics was conducted to probe the underlying mechanisms. As a result, long-term exposure to isoflurane anesthesia caused memory impairment and an increase in hippocampal 5-HT7R mRNA expression, which could be attenuated by SB-269970 pretreatment but not LP-211pretreatment. According to the proteomics results, the antiamnestic effect of SB-269970 pretreatment was probably attributed to its action on the gene expression of Slc6a11, Itpka, Arf3, Srcin1, and Epb41l2, and synapse organization in the hippocampus. In conclusion, 5-HT7R is involved in the memory impairment induced by long-term isoflurane anesthesia, and the prior blockade of 5-HT7R with SB-269970 protects the memory impairment. This finding may help to improve the understanding of the long-term isoflurane anesthesia-induced memory impairment and to construct potential preventive and therapeutic strategies for the adverse effects after long-term isoflurane exposure.

Protective effects of grape seed procyanidin on isoflurane-induced cognitive impairment in mice.

Context: Oxidative imbalance-induced cognitive impairment is among the most urgent clinical concerns. Isoflurane has been demonstrated to impair cognitive function via an increase in oxidative stress. GSP has strong antioxidant capacities, suggesting potential cognitive benefits.Objective: This study investigates whether GSP pre-treatment can alleviate isoflurane-induced cognitive dysfunction in mice.Materials and methods: C57BL/6J mice were pre-treated with either GSP 25-100 mg/kg/d for seven days or GSP 100-400 mg/kg as a single dose before the 6 h isoflurane anaesthesia. Cognitive functioning was examined using the fear conditioning tests. The levels of SOD, p-NR2B and p-CREB in the hippocampus were also analysed.Results: Pre-treatment with either a dose of GSP 50 mg/kg/d for seven days or a single dose of GSP 200 mg/kg significantly increased the % freezing time in contextual tests on the 1st (72.18 ± 12.39% vs. 37.60 ± 8.93%; 78.27 ± 8.46% vs. 52.72 ± 2.64%), 3rd (93.80 ± 7.62% vs. 52.94 ± 14.10%; 87.65 ± 10.86% vs. 52.89 ± 1.73%) and 7th (91.36 ± 5.31% vs. 64.09 ± 14.46%; 93.78 ± 3.92% vs. 79.17 ± 1.79%) day after anaesthesia. In the hippocampus of mice exposed to isoflurane, GSP 200 mg/kg increased the total SOD activity on the 1st and 3rd day and reversed the decreased activity of the NR2B/CREB pathway.Discussion and conclusions: These findings suggest that GSP improves isoflurane-induced cognitive dysfunction by protecting against perturbing antioxidant enzyme activities and NR2B/CREB pathway. Therefore, GSP may possess a potential prophylactic role in isoflurane-induced and other oxidative stress-related cognitive decline.

Formation of Environmentally Persistent Free Radicals on Microplastics under Light Irradiation.

Microplastics (MPs) are presumed to be inert during aging under ambient conditions. In this study, four types of virgin MPs, including polystyrene (PS), phenol-formaldehyde resin (PF), polyethylene (PE), and polyvinyl chloride (PVC), were aged under simulated solar light irradiation. Surprisingly, several environmentally persistent free radicals (EPFRs), which are considered to be a type of emerging contaminant, were detected on the irradiated PS and PF, rather than PE and PVC, by electron paramagnetic resonance (EPR) spectroscopy. Depending on the photoaging duration time, the characteristic g-factors of the EPFRs produced on PS and PF were 2.0044-2.0049 and 2.0043-2.0044, respectively. The generated EPFRs on PS and PF decayed rapidly at the initial stage and then slowly disappeared with the elapsed aging time. Analyses by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), nuclear magnetic resonance (NMR), and gel permeation chromatography (GPC) suggested that MPs might experience chemical chain scission, O2/H2O addition, and EPFR formation under the light irradiation. Accompanying with the formation of EPFRs, reactive oxygen species, such as O2•- and •OH, were also observed. The findings provide a novel insight to evaluate the potential hazards of MPs to organisms and ecosystems.

The role of CaMKII in neuropathic pain and fear memory in chronic constriction injury in rats.

Purpose/Aim of the study In this study, we sought to observe the effects of Ca2+/calmodulin-dependent protein kinase II (CaMKII) on neuropathic pain and fear memory in a rat model of chronic constriction injury (CCI). Materials and methods Rats were randomly divided into the Sham, Control, CCI and m-AIP groups. In the m-AIP group, an intrathecal injection of m-AIP, the specific antagonist of CaMKII, was given either pretreatment or posttreatment in rats. Mechanical allodynia and thermal hyperalgesia tests were used to test pain behavior, and the passive avoidance test was used to measure fear memory in rats. Results The right side of hippocampus tissues were taken at varying time points. The expression levels of CaMKII-α, pCaMKII-α, CaMKII-ß, pCaMKII-ß, NR2A, pNR2A, NR2B and pNR2B were detected by Western blot analysis. Significant pain behaviors and impaired cognitive function were shown after CCI surgery, accompanied by the upregulation of proteins in the hippocampus. Pretreatment with m-AIP appeared to provide a temporary improvement in pain and fear memory and decreased the expression of the above proteins in the hippocampus seven days after surgery. Furthermore, postoperative treatment with m-AIP provided relief for pain behavior and protein expression but did not affect fear memory. Conclusions These data suggested that CaMKII played an important role in the crosstalk between neuropathic pain and fear memory, indicating that CaMKII may be a potential therapeutic target for neuropathic pain treatment.

Effect of neuromuscular blockade on transcranial electric motor evoked potentials during surgical correction for idiopathic scoliosis under total intravenous anesthesia.

Transcranial electric motor evoked potentials (TCeMEPs) play an important role in reducing the risk of iatrogenic paraplegia. TCeMEPs could be obviously suppressed by neuromuscular blockade (NMB). The aims of this study were to examine the effects of NMB on TCeMEPs and to determine an appropriate level of partial neuromuscular blockade (pNMB) for TCeMEPs during surgical correction of idiopathic scoliosis under total intravenous anesthesia (TIVA). All patients were maintained with TIVA. The pNMB levels were classified into five phases: one or two train-of-four (TOF) counts (TOF1); three TOF counts, or T4/T1 (TOFR, T1,4, first or four twitch height of TOF) ≤ 15% (TOF2); TOFR at 16-25% (TOF3); TOFR at 26-50% (TOF4); and TOFR at 51-75% (TOF5). No neuromuscular blockade (nNMB) was achieved when TOFR was more than 75%. The absolute and relative latency, amplitude and area under curve (AUC), efficacy of TCeMEPs and rate of unexpected movement were compared among these phases. Neither the amplitude and AUC nor the efficacy of TCeMEPs were affected at TOF4-5 of abductor halluces muscles TCeMEPs (AH-TCeMEPs) or at TOF3-5 of tibialis anterior muscles TCeMEPs (TA-TCeMEPs) compared with nNMB. However, the rate of unexpected movement was increased significantly at TOF5 and nNMB compared with TOF1 and TOF4. The application of pNMB with TOFR aimed at 26-50% for AH-TCeMEPs or 16-50% for TA-TCeMEPs seems to be an appropriate regimen for TCeMEPs during surgical correction for idiopathic scoliosis under TIVA.

Polystyrene Nanoplastics-Enhanced Contaminant Transport: Role of Irreversible Adsorption in Glassy Polymeric Domain.

Nanoplastics (NPs) are becoming an emerging pollutant of global concern. A potential risk is that NPs may serve as carriers to increase the spreading of coexisting contaminants. In this study, we examined the effects of polystyrene nanoplastics (PSNPs, 100 nm), used as a model NP, on the transport of five organic contaminants of different polarity in saturated soil. The presence of low concentrations of PSNPs significantly enhanced the transport of nonpolar (pyrene) and weakly polar (2,2',4,4'-tetrabromodiphenyl ether) compounds, but had essentially no effects on the transport of three polar compounds (bisphenol A, bisphenol F, and 4-nonylphenol). The strikingly different effects of NPs on the transport of nonpolar/weakly polar versus polar contaminants could not be explained with different adsorption affinities, but was consistent with the polarity-dependent extents of desorption hysteresis. Notably, desorption hysteresis was only observed for nonpolar/weakly polar contaminants, likely because nonpolar compounds tended to adsorb in the inner matrices of glassy polymeric structure of polystyrene (resulting in physical entrapment of adsorbates), whereas polar compounds favored surface adsorption. This hypothesis was verified with supplemental adsorption and desorption experiments of pyrene and 4-nonylphenol using a dense, glassy polystyrene polymer and a flexible, rubbery polyethylene polymer. Overall, the findings of this study underscore the potentially significant environmental implication of NPs as contaminant carriers.

Novel Cu(II)-EDTA Decomplexation by Discharge Plasma Oxidation and Coupled Cu Removal by Alkaline Precipitation: Underneath Mechanisms.

Strong complexation between heavy metals and organic complexing agents makes the heavy metals difficult to be removed by classical chemical precipitation. In this study, a novel decomplexation method was developed using discharge plasma oxidation, which was followed by alkaline precipitation to treat water containing heavy metal-organic complex, that is, Cu-ethylenediaminetetraacetic acid (Cu-EDTA). The decomplexation efficiency of Cu complex reached up to nearly 100% after 60 min's oxidation by discharge plasma, which was accompanied by 82.1% of total organic carbon removal and energy efficiency of 0.62 g kWh-1. Presence of free Cu2+ favored Cu-EDTA decomplexation, whereas the presence of excessive EDTA depressed this process. Cu-EDTA decomplexation was mainly driven by the produced 1O2, O2•-, O3, and •OH by discharge plasma. Cu-EDTA decomplexation process was characterized by UV-vis, ATR-FTIR, total organic carbon, and three-dimensional fluorescence diagnosis. The main intermediates including Cu-EDDA, Cu-IDA, Cu-NTA, small organic acids, NH4+, and NO3- were identified, accompanied by Cu2+ releasing. The followed precipitation process removed 78.1% of Cu2+, and Cu-associated precipitates included CuCO3, Cu2CO3(OH)2, CuO, and Cu(OH)2. A possible pathway of Cu complex decomplexation and Cu2+ removal in such a system was proposed.

Cation-Inhibited Transport of Graphene Oxide Nanomaterials in Saturated Porous Media: The Hofmeister Effects.

Transport of negatively charged nanoparticles in porous media is largely affected by cations. To date, little is known about how cations of the same valence may affect nanoparticle transport differently. We observed that the effects of cations on the transport of graphene oxide (GO) and sulfide-reduced GO (RGO) in saturated quartz sand obeyed the Hofmeister series; that is, transport-inhibition effects of alkali metal ions followed the order of Na+ < K+ < Cs+, and those of alkaline earth metal ions followed the order of Mg2+ < Ca2+ < Ba2+. With batch adsorption experiments and microscopic data, we verified that cations having large ionic radii (and thus being weakly hydrated) interacted with quartz sand and GO and RGO more strongly than did cations of small ionic radii. In particular, the monovalent Cs+ and divalent Ca2+ and Ba2+, which can form inner-sphere complexes, resulted in very significant deposition of GO and RGO via cation bridging between quartz sand and GO and RGO, and possibly via enhanced straining, due to the enhanced aggregation of GO and RGO from cation bridging. The existence of the Hofmeister effects was further corroborated with the interesting observation that cation bridging was more significant for RGO, which contained greater amounts of carboxyl and phenolic groups (i.e., metal-complexing moieties) than did GO. The findings further demonstrate that transport of nanoparticles is controlled by the complex interplay between nanoparticle surface functionalities and solution chemistry constituents.

The Role of NR2B-CREB-miR212/132-CRTC1-CREB Signal Network in Pain Regulation In Vitro and In Vivo.

BACKGROUND: Chronic pain is a debilitating threat to human health, and its molecular mechanism remains undefined. Previous studies have illustrated a key role of cAMP response element-binding protein (CREB) in pain regulation; CREB-regulated transcription coactivator 1 (CRTC1) and microRNA212/132 (miR212/132) are also vital in synaptic plasticity. However, little is known about the interaction among these factors in pain condition. We conducted this experiment mainly to determine the crosstalk between CREB, CRTC1, and miR212/132 in vitro. Moreover, we explored the changes in hyperalgesia on chronic constrictive injury (CCI) mouse in vivo when given CREB-related adenovirus vectors, CRTC1-related adenovirus vectors, and miR212/132-locked nucleic acid (LNA). METHODS: We cultured primary neurons in the spinal cord of mouse embryos. Exogenous glutamate was added to cultured neurons to simulate in vivo pain process. Real-time quantitative polymerase chain reaction was used to determine changes of NR2B, CRTC1, CREB, and miR212/132 at the mRNA level; Western blot was used to detect p-NR2B, p-CREB, and CRTC1 at protein level. Von Frey cilia were used to study mechanical hyperalgesia in a murine model of CCI. CREB-miR (adenovirus vector interfering CREB gene), CREB-AD (adenovirus vector overexpressing CREB gene); CRTC1-miR (adenovirus vector interfering CRTC1 gene), CRTC1-AD (adenovirus vector overexpressing CRTC1 gene), and miR212/132-LNA were injected intrathecally. RESULTS: In vitro, 100 µmol/L glutamate induced p-CREB and miR212/132-LNA. CRTC1 protein was downregulated by CREB-miR and miR212/132-LNA. CRTC1 mRNA was upregulated by CREB-AD and downregulated by CREB-miR and miR212-LNA. P-CREB was upregulated by CRTC1-AD and downregulated by miR212/132. CREB mRNA was upregulated by CRTC1-AD and downregulated by CRTC1-miR. MiR212/132 was upregulated by CRTC1-AD and CREB-AD; downregulated by CREB-miR. In vivo, CRTC1-miR, CREB-miR, and miR212/132-LNA increased paw withdrawal mechanical threshold in various degrees. CONCLUSIONS: The NR2B-CREB-miR212/132-CRTC1-CREB signal network plays an important role in the regulation of pain. Intervening with any molecule in this signal network would reduce pain perception.

Regulation of the NR2B-CREB-CRTC1 Signaling Pathway Contributes to Circadian Pain in Murine Model of Chronic Constriction Injury.

BACKGROUND: Numerous clinical investigations have revealed the circadian rhythm changes in the perception of chronic pain, and most clinical chronic pain types peak in the night. However, it is still undiscovered whether circadian rhythm of pain exists in rodents and the specific mechanism that may underlie it. Our study was conducted to investigate the rhythmic changes of hyperalgesia behavior in a chronic constrictive injury (CCI) model of rodents and to explore the role of the N-methyl-d-aspartate receptor 2B (NR2B)-cAMP response element binding protein (CREB)-CREB-regulated transcription coactivator 1 (CRTC1) signaling pathway in this pain rhythm. METHODS: A CCI operation was performed to mimic clinical chronic pain. Paw mechanical withdrawal threshold and paw withdrawal thermal latency were used to test pain behavior in rats; a von Frey cilia test was used to test mechanical hyperalgesia in mice at Zeitgeber time (ZT) 4, ZT10, ZT16, and ZT22 for 14 contiguous days. The relative mRNA and protein expression of NR2B, CREB and CRTC1 in the suprachiasmatic nuclei and the dorsal horn were measured by real-time polymerase chain reaction and Western blot. CRTC1 and CREB interference adenovirus vectors were injected intrathecally at 2 time points, respectively (ZT12 and ZT0), to further explore the proper time point for pain treatment. RESULTS: During the period of chronic pain state, the pain behavior of CCI rodents showed a circadian rhythm with the peak at ZT4 or ZT10 daily. The pain thresholds were significantly different between the activity period and the rest period. The expressions of NR2B, CRTC1, and CREB at the spinal level were consistent with the pain rhythm. The intrathecal treatment with CRTC1 or CREB interference adenovirus from day 7 to day 9 after CCI surgery markedly improved pain behaviors. Nevertheless, when given at ZT0, they were both more effective at relieving peak pain than drugs given at ZT12. CONCLUSIONS: Pain behavior in the chronic pain of CCI displayed circadian rhythm and was associated with circadian secretion of pain-related receptors. The NR2B-CREB-CRTC1 signaling pathway may play a crucial role in this rhythm. Moreover, our results suggest that measures to relieve pain should be taken before pain reaches its peak.

Transport of Sulfide-Reduced Graphene Oxide in Saturated Quartz Sand: Cation-Dependent Retention Mechanisms.

We describe how the reduction of graphene oxide (GO) via environmentally relevant pathways affects its transport behavior in porous media. A pair of sulfide-reduced GOs (RGOs), prepared by reducing 10 mg/L GO with 0.1 mM Na2S for 3 and 5 days, respectively, exhibited lower mobility than did parent GO in saturated quartz sand. Interestingly, decreased mobility cannot simply be attributed to the increased hydrophobicity and aggregation upon GO reduction because the retention mechanisms of RGOs were highly cation-dependent. In the presence of Na(+) (a representative monovalent cation), the main retention mechanism was deposition in the secondary energy minimum. However, in the presence of Ca(2+) (a model divalent cation), cation bridging between RGO and sand grains became the most predominant retention mechanism; this was because sulfide reduction markedly increased the amount of hydroxyl groups (a strong metal-complexing moiety) on GO. When Na(+) was the background cation, increasing pH (which increased the accumulation of large hydrated Na(+) ions on grain surface) and the presence of Suwannee River humic acid (SRHA) significantly enhanced the transport of RGO, mainly due to steric hindrance. However, pH and SRHA had little effect when Ca(2+) was the background cation because neither affected the extent of cation bridging that controlled particle retention. These findings highlight the significance of abiotic transformations on the fate and transport of GO in aqueous systems.

The effect of NR2B subunit palmitoylation at the spinal level after chronic dorsal root ganglia compression in rats.

BACKGROUND: The NR2B subunit (N-methyl-D-aspartate receptor 2B subunit) regulates the source of pain, and it participates in the formation of central sensitization. Palmitoylation was shown to be involved in the regulation of N-methyl-D-aspartate receptor internalization. In the present study, we investigated the effects of NR2B subunit palmitoylation in a chronic dorsal root ganglia compression (CCD) rat model. METHODS: Paw mechanical withdrawal threshold and paw withdrawal thermal latency were used to assess mechanical allodynia and thermal hyperalgesia after a CCD operation and an intrathecal injection of the inhibitor of palmitoylation (2-bromopalmitate [2-BP]). The acyl-biotinyl exchange method, Western blotting, and coimmunoprecipitation were used to investigate the effects of pain processing and the expression of levels of NR2B palmitoylation and phosphorylation at the spinal level. RESULTS: CCD rats had long-lasting thermal hyperalgesia and mechanical allodynia, leading to upregulation of the level of NR2B palmitoylation and phosphorylation at the spinal level. An intrathecal treatment with 2-BP on day 14 after CCD surgery markedly improved pain behaviors and downregulated the expression of NR2B palmitoylation and phosphorylation. CONCLUSIONS: These data suggest that upregulated NR2B palmitoylation in CCD-induced neuropathic pain and intrathecal injection of 2-BP could reduce pain behaviors and NR2B phosphorylation. Our findings indicate that spinal NR2B palmitoylation is an important component of CCD-induced neuropathic pain, and it might be a potential target for chronic pain therapy.

Carbon quantum dots assisted BiFeO3@BiOBr S-scheme heterojunction enhanced peroxymonosulfate activation for the photocatalytic degradation of imidacloprid under visible light: Performance, mechanism and biotoxicity.

A novel S-scheme heterojunction photocatalyst carbon quantum dots (CQDs)/BiFeO3/BiOBr (CBB) was synthesized via a facile hydrothermal method, which was highly effective in activating peroxymonosulfate (PMS) to photodegrade imidacloprid (IMD) (one of the typical neonicotinoid insecticides (NEOs)) under visible light irradiation. Based on the physicochemical and photoelectrochemical analysis, the super photocatalytic performance of the CBB photocatalyst was contributed to the enhanced separation and transfer of photogenerated electrons (e-) and holes (h+), the activation of PMS by reactive species, and the wider light absorption range induced by CQDs. Moreover, the intermediate products and possible photodegradation pathways of IMD were confirmed through high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) detection and density functional theory (DFT) calculations. Although the photodegradation of IMD in the CBB/PMS/Vis system can be affected by the water quality parameters (i.e., acid group anions, pH, and the presence of humic acid (HA)), the synthesized CBB photocatalyst showed excellent photocatalytic performance in multiple natural water samples. This study provides a new idea to construct an effective and efficient heterojunction photocatalyst, which may have great advantages in photocatalytic degradation of NEOs and possibly other emerging contaminants in the aquatic environment.

Nicotinamide mononucleotide pretreatment improves long-term isoflurane anesthesia-induced cognitive impairment in mice.

Postoperative cognitive dysfunction (POCD) is characterized by impaired cognitive function following general anesthesia and surgery. Oxidative stress is a significant pathophysiological manifestation underlying POCD. Previous studies have reported that the decline of nicotinamide adenine dinucleotide (NAD+) -dependent sirtuin 1 (SIRT1) contributes to the activation of oxidative stress. In this study, we investigated whether pretreatment of nicotinamide mononucleotide (NMN), an NAD+ intermediate, improves oxidative stress and cognitive function in POCD. The animal model of POCD was established in C57BL/6 J mice through 6 h isoflurane anesthesia-induced cognitive impairment. Mice were intraperitoneally injected with NMN for 7 days prior to anesthesia, after which oxidative stress and cognitive function were assessed. The level of oxidative stress was determined using flow cytometry analysis and assey kits. The fear condition test and the Y-maze test were utilized to evaluate contextual and spatial memory. Our results showed that cognitive impairment and increased oxidative stress were observed in POCD mice, as well as downregulation of NAD+ levels and related protein expressions of SIRT1 and nicotinamide phosphoribosyltransferase (NAMPT) in the hippocampus. And NMN supplementation could effectively prevent the decline of NAD+ and related proteins, and reduce oxidative stress and cognitive disorders after POCD. Mechanistically, the findings suggested that protection on cognitive function mediated by NMN pretreatment in POCD mice may be regulated by NAD+-SIRT1 signaling pathway. This study indicated that NMN preconditioning reduced oxidative stress damage and alleviated cognitive impairment in POCD mice.

Long-term isoflurane anesthesia induces cognitive deficits via AQP4 depolarization mediated blunted glymphatic inflammatory proteins clearance.

Perioperative neurocognitive disorders (PND) refer to cognitive deterioration that occurs after surgery or anesthesia. Prolonged isoflurane exposure has potential neurotoxicity and induces PND, but the mechanism is unclear. The glymphatic system clears harmful metabolic waste from the brain. This study sought to unveil the functions of glymphatic system in PND and explore the underlying molecular mechanisms. The PND mice model was established by long term isoflurane anesthesia. The glymphatic function was assessed by multiple in vitro and in vivo methods. An adeno-associated virus was used to overexpress AQP4 and TGN-020 was used to inhibit its function. This research revealed that the glymphatic system was impaired in PND mice and the blunted glymphatic transport was closely associated with the accumulation of inflammatory proteins in the hippocampus. Increasing AQP4 polarization could enhance glymphatic transport and suppresses neuroinflammation, thereby improve cognitive function in the PND model mice. However, a marked impaired glymphatic inflammatory proteins clearance and the more severe cognitive dysfunction were observed when decreasing AQP4 polarization. Therefore, long-term isoflurane anesthesia causes blunted glymphatic system by inducing AQP4 depolarization, enhanced the AQP4 polarization can alleviate the glymphatic system malfunction and reduce the neuroinflammatory response, which may be a potential treatment strategy for PND.

HuR promotes triglyceride synthesis and intestinal fat absorption.

Triacylglyceride (TAG) synthesis in the small intestine determines the absorption of dietary fat, but the underlying mechanisms remain to be further studied. Here, we report that the RNA-binding protein HuR (ELAVL1) promotes TAG synthesis in the small intestine. HuR associates with the 3' UTR of Dgat2 mRNA and intron 1 of Mgat2 pre-mRNA. Association of HuR with Dgat2 3' UTR stabilizes Dgat2 mRNA, while association of HuR with intron 1 of Mgat2 pre-mRNA promotes the processing of Mgat2 pre-mRNA. Intestinal epithelium-specific HuR knockout reduces the expression of DGAT2 and MGAT2, thereby reducing the dietary fat absorption through TAG synthesis and mitigating high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and obesity. Our findings highlight a critical role of HuR in promoting dietary fat absorption.

Ionic specificity mediates the transport and retention of graphene-based nanomaterials in saturated porous media.

Transport of graphene-based nanomaterials in porous media is closely related to background cations. This study examines the impacts of ionic specificity on the mobility of graphene oxide (GO) and reduced GO (RGOs) in saturated quartz sand. The transport of GO/RGOs as affected by monovalent cation Na+ followed extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory, whereas in solutions containing multivalent cations Zn2+ and Al3+, cation bridging effect played a dominant role in the transport inhibition. Moreover, the adverse effects of the divalent cations on GO/RGOs migration obeyed the Hofmeister series, i.e. following the order of Pb2+ > Cd2+ > Zn2+. Batch adsorption experiments and DFT calculations further confirmed that cations of higher valences, and of the same valence but with larger ionic radii (smaller hydrated radii) interacted more strongly with GO/RGOs and sand grains via forming inner-sphere complexes. Thus, more favorable retention was observed through cation bridging between particles and collectors, and also via enhanced straining caused by particles aggregation. Furthermore, the sulfide-reduced GO (SR-GO) that contained more surface O-functional groups was impacted more remarkably by strong complexing cations than the pristine GO (P-GO), while the mobility of poorly functionalized irradiation-reduced GO (IR-GO) was less affected by cation bridging effect.

Transformation of graphene oxide affects photodegradation of imidacloprid in the aquatic environment: Mechanism and implication.

Graphene oxide (GO) is a representative novel carbonaceous nanomaterial, and neonicotinoid insecticides (NEOs) are currently the insecticides with the highest market share in the world. Their widespread application deservedly leads to their release to the environment. Thus, the complex interactions of these two types of organic compounds have attracted extensive attention. In this study, the effects of GO and its derivatives, reduced GO (RGO) and oxidized GO (OGO), on the photolysis of imidacloprid (IMD) (a typical NEO) under ultraviolet (UV) irradiation were systematically investigated. The results showed that the presence of the graphene-based nanomaterials (GNs) largely depressed the photodegradation of IMD, and the inhibition degree followed the order of RGO > GO > OGO. This was because the sp2 π-conjugated structure in the GNs caused light-shielding effect and attenuated the direct photolysis of IMD, even though the GNs-generated reactive oxygen species (ROS) promoted the indirect photodegradation of IMD to a certain extent. Additionally, the rich O-functionalized GO and OGO altered the photolysis pathway of IMD and induced more toxic intermediate products. These results highlight the implication of carbonaceous nanomaterials on the behavior, fate and potential risk of NEOs in aqueous systems.