Sevoflurane anesthesia is widely used in pediatric patients. Clinical studies report memory impairment in those exposed to general anesthesia early in life. DNA methylation is essential for the ...modulation of synaptic plasticity through regulating the transcription of synaptic genes. Therefore, we tested whether neonatal sevoflurane exposure affects learning and memory underlying the hippocampal DNA methylation of synaptic genes. Male Sprague-Dawley rats were exposed to 3% sevoflurane or air for 2 h daily from postnatal day 7 (P7) to P9. 5-aza-2-deoxycytidine (5-AZA), an inhibitor of DNA methyltransferases (DNMTs), was intraperitoneally injected 30 min before sevoflurane or air exposure on P7–9. The rats were euthanized 6, 12, 24 h, and 28 days after the last sevoflurane exposure, followed by the determination of global and gene-specific DNA methylation. The expression of synaptic proteins and synaptic density and the transcription of Dnmts and ten eleven translocations (Tets) in the hippocampus were measured. The ability of learning and memory was assessed using Morris water maze, novel object recognition, and intruder tests. Repeated neonatal sevoflurane exposure impaired cognitive, social, and spatial memory. The memory impairment was associated with the increased Dnmt1, Dnmt3a, and 5-methylcytosine level and the decreased Tet1 and 5-hydromethylcytosine level. Sevoflurane subsequently induced hypermethylation of
Shank2
,
Psd95
,
Syn1
, and
Syp
gene and down-regulated the expression of synaptic proteins, which finally led to the decrease of synaptic density in a time-dependent manner. Notably, 5-AZA pretreatment ameliorated learning and memory in sevoflurane-treated rats. In conclusion, neonatal exposure to sevoflurane can impair learning and memory through DNA methylation of synaptic genes.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Layered oxide cathodes usually exhibit high compositional diversity, thus providing controllable electrochemical performance for Na‐ion batteries. These abundant components lead to complicated ...structural chemistry, closely affecting the stacking preference, phase transition and Na+ kinetics. With this perspective, we explore the thermodynamically stable phase diagram of various P2/O3 composites based on a rational biphasic tailoring strategy. Then a specific P2/O3 composite is investigated and compared with its monophasic counterparts. A highly reversible structural evolution of P2/O3–P2/O3/P3–P2/P3–P2/Z/O3′–Z/O3′ based on the Ni2+/Ni3.5+, Fe3+/Fe4+ and Mn3.8+/Mn4+ redox couples upon sequential Na extraction/insertion is revealed. The reduced structural strain at the phase boundary alleviates the phase transition and decreases the lattice mismatch during cycling, endowing the biphasic electrode a large reversible capacity of 144 mAh g−1 with the energy density approaching 514 Wh kg−1.
A rational biphasic tailoring strategy to prepare layered composite cathodes with the desired phase ratio is proposed. Benefiting from the reversible phase transition within transition metal slabs and the decreased structure strain at the phase boundary of the intergrowth structure during Na extraction and insertion, the Com‐NaNMFT composite material demonstrates excellent electrochemical performance.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The
Varroa destructor
mite is a devastating parasite of
Apis mellifera
honeybees. They can cause colonies to collapse by spreading viruses and feeding on the fat reserves of adults and larvae. ...Amitraz is used to control mites due to its low toxicity to bees; however, the mechanism of bee resistance to amitraz remains unknown. In this study, we found that amitraz and its major metabolite potently activated all four mite octopamine receptors. Behavioral assays using
Drosophila
null mutants of octopamine receptors identified one receptor subtype Octβ2R as the sole target of amitraz in vivo. We found that thermogenetic activation of
octβ2R-
expressing neurons mimics amitraz poisoning symptoms in target pests. We next confirmed that the mite Octβ2R was more sensitive to amitraz and its metabolite than the bee Octβ2R in pharmacological assays and transgenic flies. Furthermore, replacement of three bee-specific residues with the counterparts in the mite receptor increased amitraz sensitivity of the bee Octβ2R, indicating that the relative insensitivity of their receptor is the major mechanism for honeybees to resist amitraz. The present findings have important implications for resistance management and the design of safer insecticides that selectively target pests while maintaining low toxicity to non-target pollinators.
In spite of the competitive performance at room temperature, the development of sodium‐ion batteries (SIBs) is still hindered by sluggish electrochemical reaction kinetics and unstable ...electrode/electrolyte interphase under subzero environments. Herein, a low‐concentration electrolyte, consisting of 0.5M NaPF6 dissolving in diethylene glycol dimethyl ether solvent, is proposed for SIBs working at low temperature. Such an electrolyte generates a thin, amorphous, and homogeneous cathode/electrolyte interphase at low temperature. The interphase is monolithic and rich in organic components, reducing the limitation of Na+ migration through inorganic crystals, thereby facilitating the interfacial Na+ dynamics at low temperature. Furthermore, it effectively blocks the unfavorable side reactions between active materials and electrolytes, improving the structural stability. Consequently, Na0.7Li0.03Mg0.03Ni0.27Mn0.6Ti0.07O2//Na and hard carbon//Na cells deliver a high capacity retention of 90.8 % after 900 cycles at 1C, a capacity over 310 mAh g−1 under −30 °C, respectively, showing long‐term cycling stability and great rate capability at low temperature.
This work constructs a monolithic and amorphous electrode/electrolyte interphase at low temperature which is thin, stable, and contains more organic components, facilitating fast Na+ kinetics, enabling sodium‐ion batteries to achieve long‐term cycling performance and great rate capability at −30 °C.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Lithium-ion batteries (LIBs) are at the forefront of energy storage and highly demanded in consumer electronics due to their high energy density, long battery life, and great flexibility. However, ...LIBs usually suffer from obvious capacity reduction, security problems, and a sharp decline in cycle life under low temperatures, especially below 0 °C, which can be mainly ascribed to the decrease in Li
diffusion coefficient in both electrodes and electrolyte, poor transfer kinetics on the interphase, high Li
desolvation barrier in the electrolyte, and severe Li plating and dendrite. Targeting such issues, approaches to improve the kinetics and stability of cathodes are also dissected, followed by the evaluation of the application prospects and modifications between various anodes and the strategies of electrolyte design including cosolvent, blended Li salts, high-concentration electrolyte, and additive introduction. Such designs elucidate the successful exploration of low-temperature LIBs with high energy density and long lifespan. This review prospects the future paths of research for LIBs under cold environments, aiming to provide insightful guidance for the reasonable design of LIBs under low temperature, accelerating their widespread application and commercialization.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Oxycodone is a highly prescribed opioid and its abuse has been rampant. Accumulating evidence shows that the cannabinoid CB1 receptor (CB1R) plays a key role in mediating rewarding effects to ...opioids. However, the downstream signalling of CB1R induced by oxycodone remains unclear. The neuropeptide oxytocin is well known as a potential remedy for drug addiction. Thus, our study aims to explore the mechanism of oxycodone‐induced learning and memory deficits underlying the endocannabinoid system (ECS) and the effect of oxytocin. Rats were intraperitoneally injected with oxycodone once a day for eight consecutive day. Novel object recognition, resident‐intruder and Morris Water Maze tests were employed to assess the cognitive, social and spatial memory of the rats after oxycodone withdrawal. The (co‐)expression of CB1R, cyclin‐dependent kinase 5 (Cdk5), regulatory protein p25, tau and phosphorylated tau was measured 1 day after the last behavioural test. The histopathological staining and synaptic density in the hippocampus were observed as well. We found that oxycodone upregulated the expression of p‐GSK3β, co‐expression of p‐Cdk5 and p25 through CB1R. This finding was accompanied by elevation of pSer396, pSer404 in the tau, and reduction of the number of neurons, dendritic spines and synaptic density in the hippocampus. Furthermore, i.c.v. treatment with oxytocin ameliorates memory deficits in oxycodone‐treated rats through inhibition of the ECS. We propose further studies on the clinical use of this neuropeptide, which may potentially cure drug addiction.
Oxytocin may ameliorate cognitive, social and spatial memory by rebalancing the ECS dysregulation in oxycodone‐treated rats.
Full text
Available for:
DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
FOXP3 single nucleotide polymorphisms (SNPs) were recently elucidated to influence the development of preeclampsia (PE), but the results on this issue still remained controversial. Thus, a ...meta‐analysis was implemented to systematically investigate the roles of FOXP3 SNPs in PE.
Methods
Eligible publications were identified by retrieving relevant electronic databases. Meanwhile, the association intensity was estimated by calculating odds ratios (ORs) and 95% confidence intervals (CIs) in various genetic models.
Results
Totally eight investigations involving 3446 subjects were enrolled in the final meta‐analysis. The AC and AC + CC genotypes of FOXP3 rs3761548 were related to the susceptibility of PE in over‐dominant (OR = 1.19, 95%CI = 1.02‐1.38, P = 0.03) and recessive (OR = 0.59, 95% CI: 0.36‐0.97, P = 0.04) models. Furthermore, correlation between rs2232365 and PE was observed in recessive model (GG vs. GA + AA) (OR = 0.79, 95%CI: 0.65‐0.97, P = 0.03). Moreover, rs2232365 GA and GG + GA genotypes were associated with the severity of PE. However, rs4824747, rs3761547 and rs2280883 polymorphisms had no significant impact on PE susceptibility.
Conclusions
FOXP3 rs3761548 and rs2232365 SNPs influenced the PE susceptibility and therefore may be potential biomarkers for prediction of PE risk.
Full text
Available for:
DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Oxycodone is one of the most commonly used analgesics in the clinic. However, long‐term use can contribute to drug dependence. Accumulating evidence of changes in DNA methylation after opioid relapse ...has provided insight into mechanisms underlying drug‐associated memory. The neuropeptide oxytocin is reported to be a potential treatment for addiction. The present study sought to identify changes in global and synaptic gene methylation after cue‐induced reinstatement of oxycodone conditioned place preference (CPP) and the effect of oxytocin. We analyzed hippocampal mRNA of synaptic genes and also synaptic density in response to oxycodone CPP. We determined the mRNA levels of DNA methyltransferases (Dnmts) and ten‐eleven translocations (Tets), observed global 5‐methylcytosine (5‐mC) and 5‐hydroxymethylcytosine (5‐hmC) levels, and measured DNA methylation status of four synaptic genes implicated in learning and memory (Arc, Dlg1, Dlg4, and Syn1). Both synaptic density and the transcription of 15 hippocampal synaptic genes significantly increased following cue‐induced reinstatement of oxycodone CPP. Oxycodone relapse was also related to markedly decreased 5‐mC levels and decreased transcription of Dnmt1, Dnmt3a, and Dnmt3b; in contrast, 5‐hmC levels and the transcription of Tet1 and Tet3 were increased. Oxycodone exposure induced DNA hypomethylation at the exons of the Arc, Dlg1, Dlg4, and Syn1 genes. Intracerebroventricular (ICV) administration of oxytocin (2.5 μg/μl) specifically blocked oxycodone relapse, possibly by inhibition of Arc, Dlg1, Dlg4, and Syn1 hypomethylation in oxycodone‐treated rats. Together, these data indicate the occurrence of epigenetic changes in the hippocampus following oxycodone relapse and the potential role of oxytocin in oxycodone addiction.
Global hypomethylation is involved in cue‐induced reinstatement of oxycodone CPP. DNA hypomethylation at the exon of synaptic genes is related to drug memory. Oxytocin blocks oxycodone relapse.
Full text
Available for:
DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Large post-traumatic tibial bone defects combined with soft tissue defects are a common orthopedic clinical problem associated with poor outcomes when treated using traditional surgical methods. The ...study was designed to investigate the safety and efficacy of trifocal bone transport (TFT) and soft-tissue transport with the Ilizarov technique for large posttraumatic tibial bone and soft tissue defects.
We retrospectively reviewed 31 patients with massive posttraumatic tibial bone and soft tissue defects from May 2009 to May 2016. All of the eligible patients were managed by TFT and soft-tissue transport. The median age was 33.4 years (range, 2-58 years). The mean defect of bone was 11.87 cm ± 2.78 cm (range, 8.2-18.2 cm) after radical resection performed by TFT. The soft tissue defects ranged from 7 cm × 8 cm to 24 cm × 12 cm. The observed results included bone union time, wound close time and true complications. The Association for the Study and Application of the Method of Ilizarov (ASAMI) scoring system was used to assess bone and functional results and postoperative complications were evaluated by Paley classification.
The mean duration of follow-up after frame removal was 32 months (range, 12-96 months). All cases achieved complete union in both the elongation sites and the docking sites, and eradication of infection. The mean bone transport time was 94.04 ± 23.33 days (range, 63.7-147 days). The mean external fixation time was 22.74 ± 6.82 months (range, 14-37 months), and the mean external fixation index (EFI) was 1.91 ± 0.3 months/cm (range, 1.2-2.5 months/cm). The bone results were excellent in 6 patients, good in 14 patients, fair in 8 patients and poor in 3 patients. The functional results were excellent in 8 patients, good in 15 patients, fair in 5 patients and poor in 3 patients.
TFT, in conjunction with soft tissue transport technique, can give good results in most patients (in this article, good and excellent results were observed in 64% of patients). Soft tissue transport is a feasible method in providing good soft tissue coverage on the bone ends. Although it has no advantages over microvascular techniques, it might be an good alternative in the absence of an experienced flap surgeon. Nonetheless, high-quality controlled studies are needed to assess its long-term safety and efficacy.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Histamine H2 receptor antagonists (H2RAs) were widely used to inhibit gastric acid secretion, but its association with adverse events remains controversial and unclear. We conducted an umbrella ...review of meta‐analyses to systematically assess the quality and credibility of the correlations between H2RA use with the risk of adverse outcomes through searching 4 major databases from inception to April 30, 2022. Forty‐six individual meta‐analyses were identified, including 29 meta‐analyses of observation studies with 32 unique outcomes and 19 meta‐analyses of randomized controlled trials with 3 unique outcomes for comparing the H2RA versus non‐H2RA group. A Measurement Tool to Assess Systematic Reviews 2 rating for the included meta‐analyses showed that 4 of 46 meta‐analyses were assigned as high scores, 3 were assigned as “moderate,” and 25 were assigned as low scores. Grading of Recommendations Assessment, Development and Evaluation assessment for combined results demonstrated that 6 outcomes were rated as “moderate,” 9 outcomes were rated as “low,” and 17 outcomes were rated as “very low.” We confirmed significant associations of H2RA use with pneumonia, peritonitis, necrotizing enterocolitis, Clostridium difficile infection, liver cancer, gastric cancer, and hip fracture diseases. No associations for colorectal cancer, melanoma, kidney cancer, lung cancer, or common reproductive system cancer or renal, neurological, and cardiovascular system diseases were observed. We found a variety of evidence for the associations between H2RAs and adverse outcomes, which would give clinicians more positive guidance on prescription of H2RAs in clinical practice.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
PDF
