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Purpose: The purpose of the paper is to investigate the impact of various types of intergovernmental fiscal transfers on local public education expenditure at the county level in China and to estimate the leakage of categorical subsidies for rural compulsory education. Design/Approach/Methods: It is a quantitative study. The paper constructs a quantile regression model and adopt data collected in 2007 for 1,985 counties in China to examine the impact of relevant fiscal transfers. Findings: The results reveal that most intergovernmental fiscal transfers exert a substitution effect on the local education expenditure, whereas subsidies for rural compulsory education from the Central Government have a crowding-out effect on education investments from local financial resources. Although the subsidy program generally narrows the education expenditure disparity across counties, there are heterogeneous effects across different regions. Originality/Value: The paper estimates and compares the impact of fiscal transfers on both the level and disparity of local public education in different regions, and provides a possible explanation for the crowding-out effect of fiscal transfers in China.

Supercapacitors display promising electrochemical performance with high power density and excellent cycle stability. However, their low energy density limits their advancement in a broader range of applications. To enhance their energy density, we proposed self-assembled spinel NiMn2S4 nanoflakes grown on nickel foam which we successfully prepared by a facile hydrothermal method. The NiMn2S4 electrode delivers a high capacitance of 2096.7 F g−1 at 1.0 A g−1, with an exceptional rate capability (~720.6 F g−1 at a very high current density of 100 A g−1) and good cycle stability (~85.1% retention of the initial capacitance after 7000 cycles with the Coulombic efficiency around 100%). The as-fabricated asymmetric supercapacitors based on NiMn2S4 nanoflakes//active carbon demonstrate an energy density of 73.6 W h kg−1 at 800.5 W kg−1 and adequate cycling performance of ~84.6% capacitance retention at 15 A g−1 after 10000 cycles. The results reveal that the nanostructured NiMn2S4 is an excellent electrode material for high-performance energy storage applications. [ABSTRACT FROM AUTHOR]

Background: Due to the absence of direct comparisons of different therapeutic drugs in preventing opioid-induced cough (OIC) during the induction of general anesthesia, clinicians often faced difficulties in choosing the optimal drug for these patients. Hence, this network meta-analysis was conducted to solve this problem. Methods: Online databases, including Pubmed, Embase, Web of Science, Cochrane, and Google Scholar, were searched comprehensively to identify eligible randomized controlled trials (RCTs), up to March 15th, 2021. Within a Bayesian framework, network meta-analysis was performed by the "gemtc" version 0.8.2 package of R-3.4.0 software, and a pooled risk ratio (RR) associated with 95% credible interval (CrI) was calculated. Results: A total of 20 RCTs were finally enrolled, and the overall heterogeneity for this study was low to moderate. Traditional pair-wise meta-analysis results indicated that all of the five drugs, namely, lidocaine, ketamine, dezocine, butorphanol, and dexmedetomidine could prevent OIC for four clinical outcomes, compared with the placebo (all p-values < 0.05). Moreover, dezocine had the best effect, compared with that of the other drugs (all p-values < 0.05). Network meta-analysis results suggested that the top three rank probabilities for four clinical outcomes from best to worst were dezocine, butorphanol, and ketamine based on individual/cumulative rank plots and surface under the cumulative ranking curve (SUCRA) probabilities. The node-splitting method indicated the consistency of the direct and indirect evidence. Conclusions: Our results indicated that all of these five drugs could prevent OIC compared with the placebo. Moreover, the top three rank probabilities for four clinical outcomes from best to worst were dezocine, butorphanol, and ketamine. Our results were anticipated to provide references for guiding clinical research, and further high-quality RCTs were required to verify our findings. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021243358]. [ABSTRACT FROM AUTHOR]

Background: CACNA1C, as a type of voltage-dependent calcium ion transmembrane channel, played regulatory roles in the development and progress of multiple tumors. This study was aimed to analyze the roles of CACNA1C in ovarian cancer (OC) of overall survival (OS) and to explore its relationships with immunity. Methods: Single gene mRNA sequencing data and corresponding clinical information were obtained from The Cancer Genome Atlas Database (TCGA) and the International Cancer Genome Consortium (ICGC) datasets. Gene set enrichment analysis (GSEA) was used to identify CACNA1C-related signal pathways. Univariate and multivariate Cox regression analyses were applied to evaluate independent prognostic factors. Besides, associations between CACNA1C and immunity were also explored. Results: CACNA1C had a lower expression in OC tumor tissues than in normal tissues (P < 0.001), with significant OS (P = 0.013) and a low diagnostic efficiency. We further validated the expression levels of CACNA1C in OC by means of the ICGC dataset (P = 0.01), qRT-PCR results (P < 0.001) and the HPA database. Univariate and multivariate Cox hazard regression analyses indicated that CACNA1C could be an independent risk factor of OS for OC patients (both P < 0.001). Five significant CACNA1C-related signaling pathways were identified by means of GSEA. As for genetic alteration analysis, altered CACNA1C groups were significantly associated with OS (P = 0.0169), progression-free survival (P = 0.0404), disease-free survival (P = 0.0417) and disease-specific survival (P = 9.280e-3), compared with unaltered groups in OC. Besides, CACNA1C was dramatically associated with microsatellite instability (MSI) and immunity. Conclusions: Our results shed light on that CACNA1C could be a prognostic predictor of OS in OC and it was closely related to immunity. [ABSTRACT FROM AUTHOR]

AbstractTheaflavins, a major kind of component in black tea, have been reported to show a variety of biological activities and health effects. However, the unstable chemical properties, low bioavailability and unclear metabolism pathways of theaflavins have left much to be desired in terms of its specific efficacy and applications. This paper provides a comprehensive knowledge on the digestion, absorption, metabolism, distribution and excretion of theaflavins. We find that pH-dependent stability, efflux transport proteins are closely related to the low absorption rate and low bioavailability of theaflavins. When pass through the gastrointestinal tract, TFDG, TF2A and TF2B are gradually degraded to TF1, and release gallic acid. Then, the theaflavins skeleton are degraded into small molecular phenolic substances under the action of enzymes and microorganisms. In addition, theaflavins are widely distributed in the human body including brain, lung, heart, kidney, liver, blood tissue in a low content and can be excreted through feces. However, the influence of digestive enzymes barrier and gut microbial barrier on theaflavins are still unclear. Importantly, most findings are reported by in vitro methods and animal experiments, the metabolites and metabolic pathways of theaflavins in human body are not fully understood and need to be further investigated. We hope to lay a theoretical basis for exploring methods to improve the bioavailability of theaflavins and expanding the application of theaflavins in health foods as well as pharmaceuticals. [ABSTRACT FROM AUTHOR]

Background: Exploring the effective therapy for neonatal hypoxic-ischemic brain injury is an important goal. This study was designed to investigate how dexmedetomidine (DEX) contribute to hypoxic brain injury. Methods: Developing Sprague-Dawley rat models of hypoxia/reoxygenation (H/R) injury were constructed to simulate neonatal hypoxic brain injury for DEX treatment. Immunohistochemistry and western blot were performed to measure neuroglobin (Ngb) protein expression in hippocampal tissues. Hippocampal neuron injury and apoptosis were detected by Nissl staining and TUNEL assay, respectively. A Morris water maze (MWM) test was performed to evaluate the long-term learning and memory function. Results: The expression of Ngb was increased following H/R model establishment and up-regulated by medium and high doses of DEX, but not up-regulated by low doses of DEX. Medium and high doses of DEX alleviated the H/R injury as well as induced the reduction of Nissl bodies and apoptosis. Besides, medium and high doses of DEX down-regulated cytosolic Cyt-c, Apaf-1, and caspase-3 in H/R injury model. MWM test showed that medium and high doses of DEX significantly shortened the escape latency and enhanced the number of platform crossings. However, low doses of DEX have no effect on Nissl bodies, mitochondrial apoptosis, expression of apoptosis-related proteins and long-term learning functions. Conclusions: DEX induced Ngb expression in H/R rat models. The neuroprotection of DEX-mediated Ngb up-regulation may be achieved by inhibiting neuronal apoptosis through the mitochondrial pathway. Findings indicated that DEX may be useful as an effective therapy for neonatal hypoxic brain injury. [ABSTRACT FROM AUTHOR]

To investigate the mechanism dexmedetomidine in relieving the neurotoxicity of a developing brain induced by sevoflurane. Sprague-Dawley rats, 6 days old, were randomly divided into three groups. Rats in the control group were inhaled with air after injection of normal saline; rats in the sevoflurane group were injected with normal saline and inhaled with 3% sevoflurane for 2 h in three consecutive day; rats in the dexmedetomidine group were inhaled with 3% sevoflurane after intraperitoneal injection of dexmedetomidine 25 μg/kg. WB results showed that mBDNF, pTrkB/TrkB, and CREB were significantly decreased in the hippocampus of the sevoflurane group, which are significantly upregulated in the dexmedetomidine group. In the sevoflurane group, proBDNF, P75NRT, and RhoA were significantly increased, which were significantly lower than those in the dexmedetomidine group than those in the sevoflurane group. The expression BDNF was downregulated in the sevoflurane group, while the proBDNF was upregulated in the sevoflurane group. In the Morris water maze test, the escape latency of the sevoflurane group was significantly prolonged. In sevoflurane groups, the number of crossing platform was significantly reduced, the synaptic protein decreased significantly, and this effect was reversed in rats of the dexmedetomidine group. Dexmedetomidine could reduce synaptic plasticity decline in developing rats induced by sevoflurane, through downregulating the proBDNF-p75NTR-RhoA pathway and upregulating BDNF-TrkB-CREB. [ABSTRACT FROM AUTHOR]

The magneto-optical Kerr effects in magnetic multilayered structures containing double-negative metamaterials are investigated by using 4×4 transfer-matrix method. The azimuth rotations and the figure of merit of the magneto-optical effects are calculated as a function of the thickness, permeability, and permittivity of the layers. It is shown that the magneto-optical effects are not only enhanced largely for the present system in comparison with those in the magnetic multilayered structures containing general metal materials but a giant Kerr rotation near 90° is also observed when the thickness of the sample is far less than the resonant wavelength. The physical origination for such a phenomenon is also analyzed. This means that we can obtain large magneto-optical Kerr effects at very thin magnetic film by using the double-negative metamaterials, which benefit the application in magnetic-optical recording. [ABSTRACT FROM AUTHOR]

Background: About 2% of pregnant women receive non-obstetric surgery under general anesthesia each year. During pregnancy, general anesthetics may affect brain development of the fetus. This study aimed to investigate safe dosage range of isoflurane. Methods: Forty-eight SpragueDawley (SD) pregnant rats were randomly divided into 3 groups and inhaled 1.3% isoflurane (the Iso1 group), 2.0% isoflurane (the Iso2 group) and 50% O2 alone (the control group) for 3 h, respectively. Their offsprings were subjected to Morris water maze at day 28 and day 90 after birth to evaluate learning and memory. The expression of cAMP-response element binding protein (CREB) and phosphorylated cAMP-response element binding protein (p-CREB) was detected in the hippocampus dentate gyrus. Results: Less offsprings of Iso2 group were able to cross the platform than that of the control group (P < 0.05). Accordingly, the Iso2 offsprings expressed p-CREB mainly in the subgranular zone in contrast to the whole granular cell layer of hippocampus dentate gyrus as detected in the Iso1 and control offsprings; the expression level of pCREB was also lower in the Iso2 than Iso1 or control offsprings (P < 0.05). Conclusion: Inhalation of isoflurane at 1.3% during pregnancy has no significant influence on learning and memory of the offspring; exposure to isoflurane at 2.0% causes damage to spatial memory associated with inhibition of CREB phosphorylation in the granular cell layer of hippocampus dentate gyrus. [ABSTRACT FROM AUTHOR]

Growth arrest and DNA damage-inducible 45β (GADD45β) belongs to the GADD45 family which is small acidic proteins in response to cellular stress. GADD45β has already been reported to have excellent capabilities against cancer, innate immunity and neurological diseases. However, there is little information regard GADD45β and non-alcoholic fatty liver disease (NAFLD). In the current work, we found that the expression of GADD45β was markedly decreased in the livers of NAFLD patients via analyzing Gene Expression Omnibus (GEO) dataset and in mouse model through detecting its mRNA in high-fat-high-fructose diet (HFHFr)-fed mice. Moreover, the results from in vivo experiment demonstrated that overexpression of GADD45β by AAV8-mediated gene transfer in HFHFr-fed mouse model could reduce the level of serum and hepatic triglyceride (TG), and alleviate insulin resistance. Subsequently, by combining immunoprecipitation (IP) and mass spectrometry, we identified that HSP72 directly interacted with GADD45β to prevent GADD45β from being degraded by the proteasome pathway. Finally, the benefits of GADD45β in regulating key factors of TG synthesis and insulin signaling pathway were abolished after HSP72 knockdown. In conclusion, GADD45β stabilized by the interaction with HSP72 could alleviate the NAFLD-related pathologies, suggested it might be a potential target for the treatment of NAFLD. [Display omitted] [ABSTRACT FROM AUTHOR]

As a general anesthetic widely used in surgical, sevoflurane has been shown to cause cognitive and memory deficits in the elderly. It's important to find out agents that can counteract sevoflurane-induced cognitive dysfunction. This study is aimed to investigate the effect of lovastatin on sevoflurane-induced cognitive impairment in aged rats and reveal the potential mechanisms. BV-2 cells, rat hippocampal neurons or male aged rats were exposed to 2% sevoflurane for 5 h. The cells were pretreated with 10 μM lovastatin. The rats were intraperitoneally injected with 5 mg/kg/day lovastatin for three days. The results showed that lovastatin enhanced exosomal IDE secretion from sevoflurane-exposed BV-2 cells and promoted Aβ degradation. Lovastatin treatment also inhibited the increased expressions of β-secretase 1 (BACE1) and γ-secretase in hippocampal neurons under sevoflurane exposure in vitro. In animal experiments, the discrimination index in novel object recognition test and percentage of spontaneous alternation in Y-maze test were significantly elevated after lovastatin administration. In addition, Aβ plaque area and contents of soluble Aβ 1-40 and Aβ 1-42 in the hippocampal tissues were decreased upon lovastatin treatment. Furthermore, lovastatin reversed sevoflurane-induced Aβ accumulation via up-regulating IDE expression, and down-regulating amyloid precursor protein (APP)-related protein expression (β-C-terminal fragment (CTF), BACE1 and γ-secretase). In conclusion, lovastatin alleviates sevoflurane-induced cognitive deficient in aged rats via promoting Aβ degradation and reducing Aβ production. Lovastatin may be beneficial in preventing anesthetic-induced cognitive impairment. • Lovastatin promoted Aβ degradation in vitro and in vivo. • Lovastatin improved sevoflurane-induced cognitive disorder. • Lovastatin increased IDE secretion from BV-2 cells via an exosome secretory pathway. [ABSTRACT FROM AUTHOR]

Abstract: Propagation properties of electromagnetic waves in a one-dimension random system containing left-handed-material are studied by the transfer matrix method. The statistics of the Lyapunov exponent and its variance of the transmitted waves are also analyzed. The nonlocalized modes are not only found in such a disordered system, the Anderson localization states with short localization length can also be easily realized due to the existence of low frequency resonant gap. Furthermore, our results also show that a single-parameter scaling is generally inadequate even for the complete random system with negative-n materials when the frequency we consider is located in a gap. [Copyright &y& Elsevier]

Exposure to general anesthesia in early childhood may lead to adverse effects on adolescent neurocognition. This study investigated the effects of multiple inhalations of sevoflurane on long-term learning and memory in developing rats, and explored the mechanistic role of the tissue plasminogen activator (tPA)/plasminogen activator inhibitor-1 (PAI-1) fibrinolysis system and its regulatory relationship with the brain derived neurotrophic factor (BDNF) by activation of tropomysin related kinase B (TrkB). After rats were inhaled with sevoflurane for 2 h/d for three days, the expression levels of tPA, PAI-1, BDNF, its precursor(proBDNF), TrkB and phosphorylation of TrkB (p-TrkB) were detected at different time points. After 28 d, Morris water maze was used to examine learning and memory function; Golgi staining was used to investigate synaptic plasticity and synaptic-related proteins, such as Synapsin I(SYN1), growth associated protein 43(GAP-43), and postsynaptic density protein 95(PSD-95). Rats were given exogenous tPA and an inhibitor of PAI-1, TM5275. The results showed multiple inhalation of sevoflurane led to learning and memory dysfunction, downregulated the expression of the synaptic-related proteins, decreased dendritic spine density in the hippocampus, increased the expression level of proBDNF and PAI-1, and reduced expression of BDNF, tPA, and p-TrkB. Interestingly, tPA or TM5275 partially reversed the learning and memory dysfunction and the reduction of synaptic plasticity induced by sevoflurane exposure. Furthermore, they blocked the upregulation of proBDNF and PAI-1 protein expression and increased the expression of BDNF, tPA, and p-TrkB. The protective effect of tPA or TM5275 on rats following multiple sevoflurane inhalation was blocked by a TrkB inhibitor. Multiple inhalation of sevoflurane in rats inhibited the cleavage of proBDNF by disrupting the balance of the tPA/PAI-1 fibrinolysis system. This blocked the activation of the downstream TrkB signaling pathway and reduced hippocampal synaptic plasticity, leading to long-term learning and memory dysfunction. Therefore, Sevoflurane exposure could lead to learning and memory dysfunction by inhibiting BDNF cleavage via breaking the balance of tPA/PAI-1. • Learning and memory dysfunction after multiple sevoflurane exposure was caused by decreased tPA activity in hippocampus. • Sevoflurane can elevate PAI-1 expression. • Sevoflurane can inhibite the conversion of proBDNF to mature BDNF as well as the activation of TrkB. • TM5275 and tPA can be used to treat the brain injury caused by sevoflurane. [ABSTRACT FROM AUTHOR]

(5 R)-5-hydroxytriptolide (LLDT-8) is a triptolide analog with excellent capability against cancers, cerebral ischemic injury and rheumatoid arthritis. Here, we discovered its hepatoprotective effects in a mouse model of non-alcoholic fatty liver disease (NAFLD) by ameliorating liver lipid accumulation. Male C57BL/6J mice were fed with a high-fat/high-fructose (HFHFr) diet for 29 weeks to induce the pathological phenomena of NAFLD. Then the mice were treated with LLDT-8 (0.5mg/kg and 1mg/kg) or Vehicle for 8 weeks. Finally, the serum biochemical indexes, liver histological features, fatty acids (FAs) profile and related gene expression in liver were detected to investigate the effect of LLDT-8 on lipid accumulation and its possible mechanism. LLDT-8 treatment significantly inhibited hepatic injury featured by the decrease of serum alanine aminotransferase (ALT) and aspartate transaminase (AST), the lessening of hepatic ballooning and macrovesicular steatosis. Moreover, LLDT-8 could downregulate the expression of stearoyl-CoA desaturase 1 (SCD1), which further led to the lower ratios of C16:1/C16:0 and C18:1/C18:0 and thus inhibited lipid synthesis. LLDT-8 treatment also could upregulate liver peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase 1a (Cpt1a), peroxisomal acyl-CoA oxidase 1 (Acox1), long-chain acyl-CoA dehydrogenase (Acadl) and medium-chain acyl-CoA dehydrogenase (Acadm) expression levels involved in fatty acids oxidation (FAO) and markedly promoted lipolysis. Our results provide a novel application of LLDT-8 in improving NAFLD. [ABSTRACT FROM AUTHOR]

Theaflavins (TFs) are a kind of bioactive compound that formed during the fermentation stage of black tea. TFs play a vital role both in the sensory quality and the biological activity of black tea. However, the complex composition of black tea and the low content of TFs in black tea (0.3%–0.7%) make the technology for the preparation of high‐purity TFs a great challenge. This review provides an updated overview for extracting, synthesizing and purifying of TFs. Molecular imprinting technology, an efficient method for extracting bioactive compounds, will be a promising method for the preparation of TFs with high purity. Overall, this review can provide a scientific basis and technical support for the preparation of TFs with high purity and will be helpful for the in‐depth development and further research of TFs. [ABSTRACT FROM AUTHOR]

• EAAT2 expression in hippocampus reduced after H/R injury. • Midazolam alleviated H/R-induced apoptosis and learning and memory impairment. • Midazolam reversed the decreased expression of EAAT2 induced by H/R injury. • Involvement of EAAT2 in the neuroprotective effect of midazolam on H/R injury. Excitotoxicity is one of the main mechanisms related to hypoxia/reoxygenation (H/R) injury. Excitatory amino acid transporter (EAAT)2 mainly distributes on astrocytes and plays an important role on glutamate reuptake and glutamate homeostasis. Midazolam has a neuroprotective effect in some neuropathological conditions. The present study aimed to detect the role of EAAT2 in the neuroprotective effect of midazolam in neonatal rat brain subjected to H/R. Pretreatment with midazolam reversed H/R-induced apoptosis and downregulation of EAAT2 mRNA and protein expression in the hippocampus. Pretreatment with dihydrokainic acid (a selective inhibitor of EAAT2) exacerbated apoptosis, and thus inhibited the neuroprotective effect of midazolam against H/R injury. We demonstrated for the first time that dysregulation of EAAT2 expression may be related to the neural injury induced by H/R in rat pups, and pretreatment with midazolam attenuated apoptosis and improved learning and memory partly due to regulating EAAT2 expression. [ABSTRACT FROM AUTHOR]

PCSK9 has emerged as a promising new therapeutic target for hyperlipidemia. The efficacy of PCSK9 siRNA in clinic trials clues the feasibility of exploring more PCSK9 inhibitors based on genetic inhibition in the treatment of hyperlipidemia. MicroRNAs (miRNAs) as a class of endogenous non-coding small RNAs can regulate genes at transcriptional and/or translational level. Here, we screened miRNAs from the prediction of TargetScan database with possible inhibitory activities in PCSK9 protein level via AlphaLISA and Western blotting, in which miR-552-3p was selected out for its strongest inhibitory effect. MiR-552-3p could bind to the 3' untranslated region (3'-UTR) of PCSK9 to inhibit translation and interact with the promoter of PCSK9 to suppress transcription. Further in vitro and in vivo experiments proved the effects of miR-552-3p on PCSK9 and downstream effectors: it could increase LDLR protein level, promote LDL-C uptake in HepG2 cells and lower serum LDL-C in high fat diet (HFD)-fed mice. In conclusion, our findings firstly identified miR-552-3p as a new PCSK9 inhibitor with the dual-inhibition mechanism, which suggested the possible application of miR-552-3p in the treatment of hyperlipidemia. [Display omitted] [ABSTRACT FROM AUTHOR]

The nuclear location of miRNAs has been known for more than a decade, but the exact function of miRNAs in the nucleus has not been fully elucidated. We previously discovered that intranuclear miR-552-3p has an inhibitory role on gene transcription and contains a particular AGGTCA-like sequence, the cis-elements of the NR1 subfamily of nuclear receptors. Here, we aim to explore the potential effect of miR-552-3p and its AGGTCA-like sequence on NR1s and its possible application in improving hepatic glycolipid metabolism. RNA-seq, mass spectrometry, and bioinformatics analysis were used to reveal the possible pathways influenced by miR-552-3p. High fat-high fructose diet-fed mice and db/db mice transfected with AAV2/8-miR-552-3p were established to investigate the in vivo effects of miR-552-3p on hepatic glycolipid metabolism. Fluorescence resonance energy transfer, pull-down, electrophoretic mobility shift, and chromatin immunoprecipitation assays were performed to explore the mechanism by which miR-552-3p regulates NR1s. RT-PCR was conducted to analyse miR-552-3p levels in liver biopsies from patients with NAFLD and normal controls. MiR-552-3p could inhibit metabolic gene expression in vitro and displayed beneficial effects on glycolipid metabolism in vivo. Intranuclear miR-552-3p primarily regulated the LXRα and FXR pathways; this was achieved by its binding to the complementary sequence of AGGTCA to modulate the transcriptional activities of LXRα and FXR. Moreover, LXRα and FXR ligands could restore the effects of miR-552-3p on gene expression and glycolipid metabolism. Additionally, the hepatic miR-552-3p level was significantly decreased in liver samples from patients with NAFLD compared to normal controls. The mechanism by which miR-552-3p modulates LXRα and FXR has revealed a new method of miRNA-mediated gene regulation. In addition, the beneficial effects in vivo and clinical relevance of miR-552-3p suggest that it might be a potential therapeutic target for the treatment of glycolipid metabolic disease. Glycolipid metabolic diseases, which have become a major public health concern worldwide, are triggered by abnormalities in lipid and glucose metabolism. Herein, we show that miR-552-3p has the ability to ameliorate hepatic glycolipid metabolic diseases by modulating the transcriptional activities of LXRα and FXR in the nucleus. These findings provide evidence that miR-552-3p may serve as a potential therapeutic target. • MiR-552-3p inhibits metabolism-related gene expression by modulating the transcriptional activities of LXRα and FXR in the nucleus. • MiR-552-3p ameliorates glycolipid metabolism disorder in mouse models. • MiR-552-3p levels are reduced in the livers of patients with NAFLD. • MiR-552-3p may serve as a potential target for treatment of glycolipid metabolic disease. [ABSTRACT FROM AUTHOR]

To observe the effect of dexmedetomidine (DEX) on mitochondrial apoptosis of hippocampal neurons in hypoxia/reoxygenation (H/R) brain injury in developing rats, and to investigate its regulatory mechanism on HIF-1α/p53 signaling pathway. Hypoxia/reoxygenation model was used in this study. TUNEL assay was performed to detect cell apoptosis. Immunohistochemical analysis and Western-blotting analysis were conducted to detect Cytochrome-C (Cyt-c), APAF-1, Caspase-3, Neuroglobin (Ngb), HIF-1α and p53 expression. After 28 days, Morris water maze (MWM) was performed. 50 μg/kg DEX improved H/R-induced brain injury and inhibited mitochondrial apoptosis in rats. Western-blotting and Immunohistochemical results demonstrated that DEX could up-regulate Ngb through α 2 receptor to inhibit H/R-induced mitochondrial apoptosis. In addition, by adding inhibitors yohimbine and 2-methoxyestradiol (2ME2), we found that DEX could activate HIF-1α/p53 signaling pathway. MWM test showed that DEX could enhance long-term learning and memory of H/R brain injury rats. DEX alleviates H/R-induced brain injury and mitochondrial apoptosis in developing rats through α 2 receptor, which may be related to activation of HIF-1α/p53 signaling pathway to up-regulate the expression of Ngb. [ABSTRACT FROM AUTHOR]

Vanadium-based oxides have garnered significant attention as cathode materials for aqueous zinc-ion batteries (AZIBs) because of their high theoretical capacity and low cost. However, the limited reaction kinetics and poor long-term cycle stability hinder their widespread application. In this paper, we propose a novel approach by coinserting Ni 2+ and NH 4 + ions into V 2 O 5 ·3H 2 O, i.e., NNVO. Structural characterization shows that the coinsertion of Ni 2+ and NH 4 + not only extends the interlayer spacing of V 2 O 5 ·3H 2 O but also significantly promotes the transport kinetics of Zn 2+ because of the synergistic "pillar" effect of Ni 2+ and NH 4 + , as well as the increased oxygen vacancies that effectively lower the energy barrier for Zn 2+ insertion. As a result, the AZIBs with an NNVO electrode exhibit a high capacity of 398.1 mAh g -1 (at 1.0 A g -1 ) and good cycle stability with 89.1% capacity retention even after 2000 cycles at 5.0 A g -1 . At the same time, a highly competitive energy density of 262.9 Wh kg -1 is delivered at 382.9 W kg -1 . Considering the simple scheme and the resultant high performance, this study may provide a positive attempt to develop high-performance AZIBs.

Transdermal drug delivery is one of the least intrusive and patient-friendly ways for therapeutic agent administration. Recently, functional nano-systems have been demonstrated as one of the most promising strategies to treat skin diseases by improving drug penetration across the skin barrier and achieving therapeutically effective drug concentrations in the target cutaneous tissues. Here, a brief review of functional nano-systems for promoting transdermal drug delivery is presented. The fundamentals of transdermal delivery, including skin biology and penetration routes, are introduced. The characteristics of functional nano-systems for facilitating transdermal drug delivery are elucidated. Moreover, the fabrication of various types of functional transdermal nano-systems is systematically presented. Multiple techniques for evaluating the transdermal capacities of nano-systems are illustrated. Finally, the advances in the applications of functional transdermal nano-systems for treating different skin diseases are summarized., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Photodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species (ROS) to kill cancer cells. However, the effectiveness of PDT is greatly reduced due to local hypoxia. Hypoxic activated chemotherapy combined with PDT is expected to be a novel strategy to enhance anti-cancer therapy. Herein, a novel liposome (LCT) incorporated with photosensitizer (PS) and bioreductive prodrugs was developed for PDT-activated chemotherapy. In the design, CyI, an iodinated cyanine dye, which could simultaneously generate enhanced ROS and heat than other commonly used cyanine dyes, was loaded into the lipid bilayer; while tirapazamine (TPZ), a hypoxia-activated prodrug was encapsulated in the hydrophilic nucleus. Upon appropriate near-infrared (NIR) irradiation, CyI could simultaneously produce ROS and heat for synergistic PDT and photothermal therapy (PTT), as well as provide fluorescence signals for precise real-time imaging. Meanwhile, the continuous consumption of oxygen would result in a hypoxia microenvironment, further activating TPZ free radicals for chemotherapy, which could induce DNA double-strand breakage and chromosome aberration. Moreover, the prepared LCT could stimulate acute immune response through PDT activation, leading to synergistic PDT/PTT/chemo/immunotherapy to kill cancer cells and reduce tumor metastasis. Both in vitro and in vivo results demonstrated improved anticancer efficacy of LCT compared with traditional PDT or chemotherapy. It is expected that these iodinated cyanine dyes-based liposomes will provide a powerful and versatile theranostic strategy for tumor target phototherapy and PDT-induced chemotherapy.

The association between exposure to general anesthesia and dementia risk has been inconsistently reported across epidemiological studies. To better understand the association, we conducted a meta-analysis of epidemiological studies. PubMed and Embase were searched through April 2017. Random-effects models were used to pool association estimates. We further evaluated potential dose-response relationship. Based on literature search, seven prospective/cohort studies, 11 case-control studies, and a pooled analysis of six case-control studies were identified. Sixteen of these studies were with high quality. After pooling available risk estimates, overall no significant association between exposure to general anesthesia (yes versus no) and dementia risk was detected (odds ratio (OR) = 1.03, 95% confidence interval (CI) 0.90-1.19, p for heterogeneity < 0.001). The null association persisted in the majority of subgroup analyses, although a significant positive association was detected in studies collecting anesthesia exposure using records (OR = 1.22, 95% CI 1.01-1.47, p for heterogeneity < 0.001), a method that is less prone to bias compared with interview or questionnaire using proxy reporters. Based on the dose-response analysis of three studies, a significant nonlinear relationship between times of exposure to general anesthesia and increased risk of dementia was suggested ( p < 0.0001). Overall, this meta-analysis suggests that overall the evidence from epidemiological studies supporting a link between general anesthesia exposure and an increased dementia risk is not very strong, while an association was suggested in the studies collecting anesthesia exposure using records and those providing anesthesia exposure frequency data. Further well-designed studies are warranted to better characterize the relationship of interest., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.

The quantum radiation through the multilayer structures containing the left-handed materials is investigated based on the Green-function approach to the quantization of the phenomenological Maxwell theory. Emphasis is placed on the effect of randomness on the generation and transmission of entangled-states. It is shown that some unusual properties appear for the present systems in comparison with those of the conventional dielectric structures. The quantum relative entropy is always enhanced with the increase of random degree due to the existence of nonlocalized mode in the present systems, while the maximal entanglement can be observed only at some certain randomness for the conventional dielectric structures. In contrast to exponential decrease in the conventional systems, the entanglement degrades slowly with the increase of disorder and thickness of the sample near the nonlocalized mode after transmission through the present systems. This will benefit the quantum communication for long distances.

Relativistic energy loss and photon emission in the interaction of ideal and nonideal metamaterial cloaks with an external electron beam are studied based on the classical electrodynamics. The effects of various imperfect parameters on the efficiency of the cloak are emphasized. The energy-loss spectra and the photon emission for such structures with the different combinations of electron velocity and impact parameter are calculated. It is shown that the efficiency of nonideal electromagnetic cloaks and the effect of various nonideal parameters on the cloak invisibility can be exhibited in the electron energy loss spectroscopy. This means that the properties of cloak can be explored by scanning transmission electron microscopy.