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1.
Int J Infect Dis ; 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31442627

RESUMO

OBJECTIVES: Which catheter lock solution (CLS) works best and safe for patients with catheter-related blood infections (CRBSI) remains questionable. Therefore, we compared the efficacy of different catheter lock solutions (CLSs) for prevention of CRBSI and rank these CLSs for practical consideration. METHODS: We searched PubMed, Web of Science, Embase and MEDLINE, earlier relevant meta-analysis and reference lists of included. Primary outcome was CRBSI, and secondary outcomes were catheter-related thrombosis (CRT) and exit-site infections. We performed a network meta-analysis to estimate odds ratios (ORs) with 95% confidence interval (CI). RESULTS: Finally, 52 RCTs involving 9099 patients and evaluating 13 CLSs (alone or combination) were included. The quality of the evidence was typical of low or unclear risk of bias (45 out of 52 trials, 86.5%). In network meta-analysis, saline (odds ratio (OR) 8.44, 95% CI 2.19 to 32.46), gentamicin + citrate (2.92, 1.32 to 6.42), ethanol (5.33, 1.22 to 23.32) and cloxacillin + heparin (2.07, 1.19 to 5.49) were associated with more effect on the CRBSI than heparin. CONCLUSIONS: Our network meta-analysis showed that EDTA seemed to be the most effective for CRBSI and Exit-site infection, and cefotaxime + heparin seemed to be the most effective for CRT.

2.
Front Immunol ; 10: 1673, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379864

RESUMO

Porcine beta-defensin 2 (PBD-2) which is a member of the family of antimicrobial peptides, is widely expressed in pig organs with a broad spectrum of bactericidal activities confirmed in vitro. We previously demonstrated that transgenic (TG) pigs overexpressing PBD-2 could resist the infection by the porcine pathogen Actinobacillus pleuropneumoniae. In this study, the roles of PBD-2 in protecting against bacterial infection were further investigated. The biochemical indexes of the blood sample, body weights, histological morphologies, and weights of the organs of TG mice expressing PBD-2 were measured. Results confirmed that these mice showed normal physiological features. An assay of Salmonella Typhimurium infection was conducted on wild-type (WT) and TG mice. The TG mice possessed higher survival rate, less body weight loss, and pathological changes and smaller recovery rates of bacteria after infection with S. Typhimurium. The in vitro synthetic PBD-2 and the serum and tissue homogenates from the TG mice displayed a direct bactericidal activity. Moreover, PBD-2 could inhibit the release of the proinflammatory cytokines, including IL-6, TNF-α, IL-1ß, and IL-12, in the TG mice infected with S. Typhimurium or treated with lipopolysaccharide (LPS). The WT mice treated with PBD-2 and S. Typhimurium or LPS showed reduced levels of proinflammatory cytokines. The mouse macrophage cell line RAW 264.7 which expressed PBD-2 was constructed to detect the signal pathways affected by PBD-2. The suppressing effect of PBD-2 on the release of the proinflammatory cytokines was confirmed using RAW 264.7 either expressing PBD-2 or supplemented with PBD-2. The promoter activity and mRNA level of NF-κB were detected, and PBD-2 was shown to significantly inhibit the activation of the NF-κB pathway induced by LPS. The direct interaction of PBD-2 with TLR4 was revealed by isothermal titration calorimetry and far-Western blot in vitro and the coimmunoprecipitation of PBD-2 with TLR4 on RAW 264.7 cells. This interaction indicates one reason for the interference of NF-κB activation. Overall, this study showed that PBD-2 protected against bacterial infection through a direct bactericidal activity and alleviated inflammation by interfering with the TLR4/NF-κB pathway.

4.
Phys Chem Chem Phys ; 21(32): 17740-17745, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31367721

RESUMO

Recently, the discovery of two-dimensional transition-metal materials with non-trivial magnetic and electronic properties has spurred huge interest in investigating their applications in nanotechnology. Here, we report that the monolayer of CoBr3 possesses a quantum anomalous Hall insulating phase generated on the basis of first-principles calculations. We find that the CoBr3 monolayer is an intrinsic two-dimensional ferromagnetic material with a Curie temperature Tc = 264 K predicted from Monte Carlo simulations. The phonon spectra analysis indicates that the CoBr3 monolayer is dynamically stable. Taking into account spin-orbit coupling, this makes the electronic structure of the CoBr3 monolayer topologically non-trivial with a global band gap of 8.7 meV. The anomalous Hall conductivity calculation shows a Chern number C = 2, meaning the presence of a two edge state in nanoribbons of finite width. These findings not only add an experimentally feasible member to the quantum anomalous Hall insulator family, but also pave the way for highly promising application potentials in nanoelectronics and spintronics.

5.
Dev Comp Immunol ; 102: 103474, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31437526

RESUMO

Tyrosine kinase 2 (TYK2), a member of Janus kinase family, has been identified as a crucial protein in signal transduction initiated by interferons or interleukins in mammals. However, the function of avian TYK2 in innate immune response remains largely unknown. In this study, the full-length duck TYK2 (duTYK2) cDNA was cloned for the first time, which encoded a putative protein of 1187 amino acid residues and showed the high sequence similarity with bald eagle, crested ibis, and white-tailed tropicbird TYK2s. The duTYK2 was widely expressed in all examined tissues of healthy ducks and showed diffuse cytoplasmic localization in duck embryo fibroblasts (DEFs). Overexpression of duTYK2 significantly enhanced ISRE promoter activity and induced the expression of viperin, PKR, 2',5'-OAS, Mx and ZAP in DEFs. The C-terminal kinase domain of duTYK2 is essential for duTYK2-mediated ISRE promoter activation. Furthermore, knockdown of duTYK2 dramatically decreased duck Tembusu virus (DTMUV)-, duck enteritis virus (DEV)-, poly(I:C)- or poly(dA:dT)-induced ISRE promoter activation. Additionally, duTYK2 expression exhibited antiviral activity against DTMUV. These results indicated that duTYK2 played a critical role in duck antiviral innate immunity.

6.
Metabolism ; 100: 153956, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31394109

RESUMO

To systematically review clinical practice guidelines (CPGs) on diabetes foot and assess the consistency of recommendations, quality of CPGs and to present an evidence-map for explicating research trends and gaps. We performed a literature search on PubMed, Embase, and Web of Science, guideline databases and websites of diabetes society to include the diabetic CPGs. The basic information, recommendations for the diabetic foot, methodological quality and reporting quality of diabetic CPGs were exacted by the Excel. Four researchers evaluated the methodological and reporting quality of diabetic foot CPGs by AGREE II instrument and RIGHT checklist. R3.5.1 software was used to create all bubble plots. A total of 22 diabetic CPGs were included, eight CPGs were from different professional diabetes societies. Recommendations on diabetic foot complications involve Diabetic foot ulcer (DFU), Charcot neuropathy (CN) and Osteomyelitis (OM). Eight DFU diagnostic systems presented in 22 CPGs. According to the recommendations of diabetic CPGs, the treatment of DFU can be summarized in four major items; six recommendations on CN diagnosis and six recommendations on treatment of CN were consistent among studies. However, there were inconsistencies in three OM diagnosis recommendations and four OM treatment recommendations. Some recommendations in CPGs were not very specific and clear, and hence they were not reliable for OM diagnosis and treatment. Once these inconsistencies are resolved, validated, accurate and effective diagnosis and treatment of diabetes foot will lead to reduced costs and adverse complications. The results of this review add to our knowledge and promote the development of trustworthy CPGs on diabetes.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31435643

RESUMO

BACKGROUND: The aim of this study was to examine the trends in impairment regarding activities of daily living (ADL), physical performance and cognitive function among the oldest-old (those aged ≥80 years) in China between 1998 and 2014. METHODS: We used data on 34,297 oldest-old individuals from the seven waves of the Chinese Longitudinal Healthy Longevity Study. We estimated age, period and cohort effects on the prevalence of self-reported ADL impairment, tested physical performance and cognitive function impairment using the age-period-cohort (APC) model. RESULTS: Regarding age, the prevalence of ADL, physical and cognitive impairment were highest in the centenarians, but they did not increase with age in this population. Among the literate subgroup, the prevalence of cognitive impairment increased more rapidly with age than that in the illiterate subgroup. Regarding period, the prevalence of self-reported and tested physical impairment slowly increased between 1998 and 2014, but cognitive impairment remained stable. Regarding cohort, ADL impairment continuously decreased. However, physical and cognitive impairment remained stable after a brief decline in the early birth cohorts. CONCLUSIONS: The results suggest that the age effect is still the most obvious effect regarding several types of functional impairment. The likelihood of a younger person experiencing functional impairment may not change significantly, but ADL is likely to be amenable to improvement resulting from improved medical and social care. Therefore, increased care for the elderly may considerably improve their quality of life, particularly regarding their basic activities of daily living.

8.
Genes (Basel) ; 10(8)2019 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-31394801

RESUMO

Whole-genome sequences of four EMS (ethyl methanesulfonate)-induced eggplant mutants were analyzed to identify genome-wide mutations. In total, 173.01 GB of paired-end reads were obtained for four EMS-induced mutants and (WT) wild type and 1,076,010 SNPs (single nucleotide polymorphisms) and 183,421 indels were identified. The most common mutation type was C/G to T/A transitions followed by A/T to G/C transitions. The mean densities were one SNP per 1.3 to 2.6 Mb. The effect of mutations on gene function was annotated and only 7.2% were determined to be deleterious. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis showed 10 and 11 genes, which were nonsynonymous mutation or frameshift deletion in 48-5 and L6-5 involved in the anthocyanin biosynthesis or flavone and flavonol biosynthesis. QRT-PCR results showed that only the Sme2.5_06210.1_g00004.1, which was annotated as UFGT (Flavonoid galactosidase transferase), expression significantly decreased in the L6-5 mutant compared with the WT. Also, the Sme2.5_06210.1_g00004.1 expression was lower in the colorless eggplant compared with colorful eggplant in the natural eggplant cultivar. These results suggest that Sme2.5_06210.1_g00004.1 may play a key role in eggplant anthocyanin synthesis.

9.
J Dig Dis ; 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31448533

RESUMO

AIM: Lactulose is effective in the treatment and prevention of overt hepatic encephalopathy (OHE), but there is limited data of lactulose use on microbiota in relations to MHE recovery. The present study is to assess the efficacy of lactulose in recovery of MHE in aspects of cognitive function, QoL and impact on intestinal microbiota. METHODS: This multicenter, randomized, open label controlled trial was conducted in 11 teaching hospitals in China. Participants were randomly allocated 2:1 to receive lactulose (Gp-L), or no therapy as control (Gp-NL) for 60 days. The primary endpoint was the MHE reversal rate. Gut microbiota were compared between MHE patients and healthy volunteers, as well as lactulose-responders and non-responders. RESULTS: A total of 98 cirrhotic patients were included in the study, with 31 patients in the Gp-NL group and 67 patients in the Gp-L group. At day 60, the MHE reversal rate in Gp-L (64.18%) was significantly higher than that in Gp-NL (22.58%) (p=0.0002) with RR 0.46(95%CI 0.32, 0.67).NNT is 2.4. Further, there was significantly more improvement in physical functioning in Gp-L (4.62±6.16) than in Gp-NL (1.50±5.34) (p=0.0212). Proteobacteria was significantly higher in MHE patients compared with healthy volunteers (12.27% vs 4.65%, p<0.05). Significant differences were found between lactulose responders and non-responders in Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria. CONCLUSIONS: Treatment with lactulose significantly improves MHE recovery rate , and gut microbiota change in MHE patients can modulate the effectiveness of this therapy. Chinese Clinical Trial Register (ChiCTR) (ID: ChiCTR-TRC-12002342). This article is protected by copyright. All rights reserved.

10.
Fertil Steril ; 112(1): 89-97.e1, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277770

RESUMO

OBJECTIVE: To evaluate whether intrauterine injection of hCG before embryo transfer can improve IVF-ET outcomes. DESIGN: Meta-analysis. SETTING: Not applicable. PATIENT(S): Infertile women who underwent IVF-ET and received an intrauterine injection of hCG before ET. INTERVENTION(S): Infertile women treated with or without intrauterine hCG injection before ET. MAIN OUTCOME MEASURE(S): The primary outcomes were live birth rate (LBR), ongoing pregnancy rate (OPR), and clinical pregnancy rate (CPR), and the secondary outcomes were implantation rate (IR) and miscarriage rate (MR). Odds ratios with 95% confidence intervals (CIs) and successful ET rates were pooled to determine the effects of hCG on IVF-ET outcomes. RESULT(S): Fifteen randomized controlled trials (RCTs) with a total of 2,763 participants were included. Infertile women in the experimental group (treated with intrauterine hCG injection before ET) exhibited significantly higher LBR (44.89% vs. 29.76%), OPR (48.09% vs. 33.42%), CPR (47.80% vs. 32.78%), and IR (31.64% vs. 22.52%) than those in the control group (intrauterine injection of placebo or no injection). Furthermore, MR was significantly lower (12.45% vs. 18.56%) in the experimental group than in the control group. CONCLUSION(S): The findings of this meta-analysis indicate that intrauterine injection of hCG can improve LBR, OPR, CPR, and IR after IVF-ET cycles. In addition, different timing and dosages of hCG administration may exert different effects on IVT-ET outcomes. Notably, infertile women treated with 500 IU hCG within 15 minutes before ET can achieve optimal IVF-ET outcomes.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31350939

RESUMO

AIM: To assess the methodological and reporting quality of paediatric clinical practice guidelines (CPGs) in National Guideline Clearinghouse (NGC) using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument and Reporting Items for Practice Guidelines in Healthcare (RIGHT) standard. METHODS: We identified all published CPGs through the NGC, and search records were screened in duplicate for inclusion. Two researchers evaluated the methodological and reporting quality of paediatric CPGs using the AGREE II instrument and RIGHT standard. STATA version 12.0 and SPSS version 22.0 software were used to analyse the related data. RESULTS: A total of 50 paediatric CPGs were included. The scores for all six domains by AGREE II instrument were presented as follows: scope and purpose (85.6 ± 9.59), stakeholder involvement (69.15 ± 19.32), rigour of development (73.19 ± 17.18), clarity of presentation (78.51 ± 14.36), applicability (54.61 ± 22.63) and editorial independence (68.42 ± 13.06). In the seven domains of the RIGHT standard, the reporting rate of the recommendation domain was the lowest (52.86%).The highest reporting rate was the other information domain, which was 68%.There was a high correlation between reporting the completeness of CPGs using the AGREE II instrument and RIGHT standard (r = 0.77, P < 0.001). CONCLUSIONS: The paediatric CPGs from NGC have good quality. There was a high correlation in the completeness of reporting for paediatric CPGs using the AGREE II instrument and RIGHT standard. It could be concluded that the CPGs of good methodological quality have good reporting quality. Maybe the researcher should effectively combine the AGREE II instrument and RIGHT standard in the development process of CPGs.

12.
J Infect Dis ; 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31323094

RESUMO

BACKGROUND: This review aimed to provide constructive suggestions for the control and management of avian influenza through quantitative and qualitative evaluation of the impact of different live poultry market (LPM) interventions. METHODS: Both English and Chinese databases were searched for articles that were published on or before November 9, 2018. After extraction and assessment of the included literature, stata14.0 was applied to perform meta-analysis to explore the impacts of LPM interventions. RESULTS: A total of 19 studies were identified. In total, 224 humans, 3550 poultry, and 13,773 environment samples were collected before the intervention; 181 humans, 4519 poultry, and 9562 environments were sampled after LPM interventions. Avian influenza virus (AIV) detection rates of the LPM environment (odds ratio [OR] = 0.393; 95% confidence interval [CI], 0.262-0.589) and the incidence of human avian influenza infection (OR = 0.045; 95% CI, 0.025-0.079) were significantly lower after LPM interventions, while LPM interventions on poultry were not significantly effective (OR = 0.803; 95% CI, 0.403-1.597). CONCLUSIONS: LPM interventions can reduce human infections of avian influenza and the detection rate of AIV in market environments.

14.
Aging (Albany NY) ; 11(13): 4757-4771, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31306100

RESUMO

In pace with the development of gene sequencing technology and transcriptome research, it has been found that 70 to 90% of the human genome is transcribed into RNAs, while only 2% of RNAs encode proteins. This implies that non-coding RNAs (ncRNAs) may exert vital biological functions and a full analysis of non-coding transcriptomes is needed. Over the past decade, the advance in high-throughput sequencing and transcriptome profiling has enabled the identification of circular RNAs (circRNAs) involved in many biological processes and the occurrence and development of diseases. Accumulating evidence has revealed that circRNAs may serve as new biomarkers for diagnosis as well as provide promising therapeutic approaches and novel drug screening strategies for leukemia. A comprehensive understanding of circRNAs in leukemia is a prerequisite for the development of clinical translational research. In this review, we will discuss the general information of circRNAs and focus on the current advances in understanding the association between dysregulated circRNAs and leukemia.

15.
Mikrochim Acta ; 186(8): 580, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31352527

RESUMO

A dual-channel ratiometric method is presented for improved colorimetric and fluorometric visualization of the fungicide cymoxanil (CYM). It is based on the use of a mixture of dually emitting carbon dots (CDs) and citrate-stabilized silver nanoparticles (AgNPs). The CDs, under photoexcitation at 350 nm, display dual (blue and green) fluorescence, with peaks at 435 and 520 nm. In mixed aqueous suspension of CDs and AgNPs, the intensity of blue fluorescence of CDs is reduced due to internal filter effect (IFE). This is due to the spectral overlap between the emission of CDs and the absorption of yellow AgNPs. After the addition of CYM to the mixture, CYM triggers the aggregation of AgNPs due to electrostatic attraction and hydrogen bonding interactions. The aggregated AgNPs have an orange color with an absorption whose maximum is shifted to around 510 nm. Hence, it overlaps the green emission of CDs. This causes an IFE on the green fluorescence, while the blue fluorescence is recovered. The colorimetric is performed by ratioing the absorbances at 515 and 390 nm. The ratiometric fluorometric assay is based on ratioing the emissions at 435 and 520 nm. The assay has a wide detection range (0.01-0.55 µΜ) and a low limit of detection (2 nM at S/N = 3). The assay was applied to the determination of CYM in spiked real samples (natural river water, soil and plant epidermis). Recoveries ranged between 97 and 105%. The method enables assays to perform on-site and visual detection by observing fluorescence color shades in either aqueous solutions and on wetted filter paper strips. Graphical abstract Schematic representation of a dual (colorimetric and fluorometric) ratiometric assay for the fungicide cymoxanil (CYM). The method is based on CYM-induced aggregation of silver nanoparticles (AgNPs) and an internal filter effect which induces fluorescence (FL) changes of dually emitting carbon dots (CDs).

16.
J Mol Cell Cardiol ; 135: 40-51, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31352044

RESUMO

BACKGROUND: Seroepidemiological studies have highlighted a positive relation between CagA-positive Helicobacter pylori (H. pylori), atherosclerosis and related clinic events. However, this link has not been well validated. The present study was designed to explore the role of H. pylori PMSS1 (a CagA-positive strain that can translocate CagA into host cells) and exosomal CagA in the progression of atherosclerosis. METHODS: To evaluate whether H. pylori accelerates or even induces atherosclerosis, H. pylori-infected C57/BL6 mice and ApoE-/- mice were maintained under different dietary conditions. To identify the role of H. pylori-infected gastric epithelial cells-derived exosomes (Hp-GES-EVs) and exosomal CagA in atherosclerosis, ApoE-/- mice were given intravenous or intraperitoneal injections of saline, GES-EVs, Hp-GES-EVs, and recombinant CagA protein (rCagA). FINDINGS: CagA-positive H. pylori PMSS1 infection does not induce but promotes macrophage-derived foam cell formation and augments atherosclerotic plaque growth and instability in two animal models. Meanwhile, circulating Hp-GES-EVs are taken up in aortic plaque, and CagA is secreted in Hp-GES-EVs. Furthermore, the CagA-containing EVs and rCagA exacerbates macrophage-derived foam cell formation and lesion development in vitro and in vivo, recapitulating the pro-atherogenic effects of CagA-positive H. pylori. Mechanistically, CagA suppresses the transcription of cholesterol efflux transporters by downregulating the expression of transcriptional factors PPARγ and LXRα and thus enhances foam cell formation. INTERPRETATION: These results may provide new insights into the role of exosomal CagA in the pathogenesis of CagA-positive H. pylori infection-related atherosclerosis. It is suggested that preventing and eradicating CagA-positive H. pylori infection could reduce the incidence of atherosclerosis and related events.

17.
PLoS One ; 14(7): e0215266, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31348788

RESUMO

Tourist congestion at hot spots has been a major management concern for UNESCO World Heritage Sites and other iconic protected areas. A growing number of heritage sites employ technologies, such as cameras and electronic ticket-checking systems, to monitor user levels, but data collected by these monitoring technologies are often under-utilized. In this study, we illustrated how to integrate data from hot spots by camera-captured monitoring and entrance counts to manage use levels at a World Heritage Site in Southeastern China. 6,930 photos of a congestion hotspot (scenic outlook on a trail) were collected within the park at a 10-minute interval over 105 days from January to November 2017. The entrance counts were used to predict daily average and maximum use level at the hotspots. Results showed that the average use level at the congestion hotspot did not exceed the use limit mandated by the park administration agency. However, from 9:20 am to 12:00 pm, the use level at hotspots exceeded visitor preferred use level. Visitor use level was significantly higher at the hotspot during a major Chinese "Golden Week". The daily entrance counts significantly predicted the average and maximum use level at the hotspot. Based on our findings, park managers can achieve the management goals by permitting the corresponding number of visitors passing the entrances. The gap manifested the complexities in visitor capacity management at high-use World Heritage Sites and other protected areas and calls for innovative monitoring and management strategies.

18.
Neurochem Int ; 129: 104507, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31325476

RESUMO

Heightened activity of glycogen synthase kinase-3ß (GSK-3ß) is linked to the degeneration of dopaminergic neurons in Parkinson's disease (PD). Phytic acid (PA), a naturally occurring compound with potent antioxidant property, has been shown to confer neuroprotection on dopaminergic neurons in PD. However, the underlying mechanism remains unclear. In the present study, MPTP and MPP+ treatments were used to model PD in mice and SH-SY5Y cells, respectively. We observed reduced tissue dopamine, disrupted synaptic vesicle recycling, and defective neurotransmitter exocytosis. Furthermore, expression of GSK-3ß was upregulated while that of ß-catenin was downregulated, concentration of cytosolic calcium was increased, and expressions of two dopamine carriers, dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) were decreased. PA treatment attenuated the MPTP-induced upregulation of GSK-3ß, increase in cytosolic calcium concentration, decreases in the levels of DAT, VMAT2, tissue dopamine, and synaptic vesicle recycling. Importantly, disturbances in synaptic vesicle recycling are thought to be early events in PD pathology. These findings suggest that PA is a promising therapeutic agent to treat early events in PD.

19.
Brain Res ; 1721: 146333, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31302097

RESUMO

After associative learning, a signal induces the recall of its associated signal, or the other way around. This reciprocal retrieval of associated signals is essential for associative thinking and logical reasoning. For the cellular mechanism underlying this associative memory, we hypothesized that the formation of synapse innervations among coactivated sensory cortices and the recruitment of associative memory cells were involved in the integrative storage and reciprocal retrieval of associated signals. Our study indicated that the paired whisker and olfaction stimulations led to an odorant-induced whisker motion and a whisker-induced olfaction response, a reciprocal form of associative memory retrieval. In mice that showed the reciprocal retrieval of associated signals, their barrel and piriform cortical neurons became mutually innervated through their axon projection and new synapse formation. These piriform and barrel cortical neurons gained the ability to encode both whisker and olfaction signals based on synapse innervations from the innate input and the newly formed input. Therefore, the associated activation of sensory cortices by pairing input signals initiates their mutual synapse innervations, and the neurons innervated by new and innate synapses are recruited to be associative memory cells that encode these associated signals. Mutual synapse innervations among sensory cortices to recruit associative memory cells may compose the primary foundation for the integrative storage and reciprocal retrieval of associated signals. Our study also reveals that new synapses onto the neurons enable these neurons to encode memories to new specific signals.

20.
Mater Sci Eng C Mater Biol Appl ; 103: 109831, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31349481

RESUMO

Combination of both internal- and external-stimuli responsive strategies in nanoplatforms can maximize therapeutic outcomes by overcoming drug efflux-mediated resistance and prolonging sustained release of therapeutic payloads in controlled and sequential manner. Here, we show a light/redox dual-stimuli responsive ß-cyclodextrin (ß-CD)-gated mesoporous silica nanoparticles (MSN) that can effectively load and seal the chemotherapeutics, doxorubicin (DOX), inside MSN with a dual-capped system. The primary gatekeeper was achieved by capping ß-CD via a disulfide linkage. An azobenzene/galactose-grafted polymer (GAP) was introduced to functionalize the MSN surface through host-guest interaction. GAP not only served as a secondary non-covalent polymer-gatekeeper to further prevent molecules from leaking out, but also presented targeting ligand for engagement of the asialoglycoprotein receptor (ASGPR) on hepatocellular carcinoma (HepG2) cells. The controlled and stimuli release of DOX could be realized via dissociation of azobenzene moieties from ß-CD cage upon UV-irradiation, followed by liberation with the endogenous glutathione. The in vitro studies verified the redox-sensitive DOX release behavior, and the UV irradiation could accelerate this process to trigger DOX burst from MSN-ss-CD/GAP. Notably, the DOX@MSN-ss-CD/GAP could more efficiently deliver DOX into HepG2 cells and demonstrate enhanced cytotoxicity as compared with HeLa and COS7 cells. The smart MSN-ss-CD/GAP delivery system holds the potential for universal therapeutic uses in both biomedical research and clinical settings.

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