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1.
Talanta ; 221: 121660, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33076170

RESUMO

As a common plasma protein, alpha-fetoprotein (AFP) is widely applied as the tumor biomarker for the diagnosis of many cancers. To develop a low cost, high sensitive and high-throughput method for the determination of AFP is significant for the disease diagnosis. In this work, an immunoassay with sandwich-type structures was performed on a paper-based chip for the analysis of AFP. AFP could be captured by the primary antibodies which were immobilized on the paper by chitosan. On the secondary antibodies, the modified initiator DNAs could trigger the hybridization chain reaction to amplify the fluorescence signals for AFP. A laser-induced fluorescence detector coupled with an interface was applied to detect the targets on the paper-based chip. Under the optimized conditions, the detection limit for AFP was 1.0 pg/mL. For every test, the sample solution consumption only was 10 µL. Finally, the method was applied to determine the AFP in serum of normal person and hepatopaths with hepatic malignant tumor, chronic hepatitis B and other suspected liver diseases. The AFP could be found from all of the samples and the results were similar to that obtained by chemiluminescence immunoassay. The recoveries for AFP ranged from 93.8% to 106%, which indicated the method was reliable. The method based on paper chip had great potential in the application of AFP determination.

2.
Talanta ; 221: 121668, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33076174

RESUMO

Rapid and sensitive diagnosis of bacterial infections at early stage is of great significance for food safety monitoring as well as clinical treatment. Herein, we construct a surface-enhanced Raman scattering (SERS) nanoprobe based on M13 phages for the selective detection and inactivation of Staphylococcus aureus (S. aureus). M13 phage with specific S. aureus-binding heptapeptide displayed on the N-terminal of pIII protein is selected from phage display peptide library. The S. aureus-specific SERS probe is thus constructed by in situ growth of gold nanoparticles (AuNPs) on M13 phage surface, followed by modification with 5,5-dithiobis-(2-nitrobenzoic acid) (DTNB) as SERS active molecule. Upon the addition of this SERS probe, M13 phage selectively binds with S. aureus to induce anchoring of AuNPs on S. aureus surface, and the SERS probe-labeled S. aureus cells are collected by centrifugation for SERS detection. For the quantification of S. aureus, a linear range of 10-106 cfu mL-1 is achieved in aqueous medium. It is further demonstrated by spiking recovery in soft drinks. Furthermore, this SERS probe exhibits bactericidal capabilities towards S. aureus, which shows promising potential to serve as a multifunctional platform for simultaneous detection and inactivation of S. aureus.

3.
Mol Genet Genomic Med ; : e1518, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33002343

RESUMO

BACKGROUND: The enzyme NOP2/Sun RNA methyltransferase 2 (NSUN2) catalyzes the methylation of cytosine to 5-methylcytosine (m5C) at position 34 of tRNA(Leu; CAA) precursors containing introns that play a vital role in spindle assembly during mitosis and chromosome segregation. Biallelic variants in the NSUN2 gene cause a rare intellectual disability that has been identified only in a few Middle Eastern patients. Affected individuals usually have other deformities, including developmental delay, short stature, microcephaly, and facial dysmorphism. The aim of this study was to identify the genetic cause of three female patients from a Chinese pedigree, who presented with similar phenotype consisting of the above clinical features. METHODS: Whole-exome sequencing (WES) was used to screen for causal variants in the genome, and the candidate variants were subsequently verified using Sanger sequencing. RESULTS: WES revealed a previously unreported homozygous nonsense variant (NM_017755.5: c.1004T>A, p.Leu335*) in exon 9 of NSUN2, which was consistent with the clinical phenotype of the patients and co-segregated with the disease in their family. A comparison of this phenotype with that of patients in published reports uncovered several novel clinical features related to NSUN2 variations, including feeding difficulties, slender hands and fingers, severely restricted finger mobility, hallux valgus, varus foot, and elevated α-hydroxybutyrate dehydrogenase (HBDH). CONCLUSIONS: These are the first findings of a non-consanguineous Chinese pedigree with a homozygous NSUN2 variant. We expanded the phenotypic spectrum associated with NSUN2 variations.

5.
Chin Med J (Engl) ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33009021

RESUMO

BACKGROUND: Endometrial cancer is one of the most common malignancies of the reproductive system. Effective and cost-effective screening method for populations at high risk is not available. This study aimed to investigate specimen adequacy and the influencing factors in microscale endometrial sampling biopsy and to evaluate the diagnostic accuracy and medical cost of biopsy in endometrial cancer and atypical hyperplasia screenings in comparison with hysteroscopic endometrial biopsy. METHODS: A total of 1551 patients at high risk for endometrial lesions who required hysteroscopic endometrial biopsy from November 2017 to August 2018 were included. Microscale endometrial sampling biopsy was performed, followed by hysteroscopic endometrial biopsy. We evaluated the specimen adequacy and influencing factors of microscale endometrial sampling. Diagnostic consistency between microscale endometrial sampling biopsy and hysteroscopic endometrial biopsy was evaluated. The sensitivity, specificity, positive predictive value, and negative predictive value of microscale endometrial sampling biopsy in screening for endometrial cancer and atypical hyperplasia were analyzed, and the medical costs of the two procedures were compared. RESULTS: The specimen adequacy was 81.2%. Patient age, menopausal status, endometrial thickness, and endometrial lesion type were correlated with specimen adequacy. There was good consistency in distinguishing benign and malignant endometrial diseases between microscale endometrial sampling biopsy and hysteroscopic biopsy (kappa 0.950, 95% CI 0.925-0.975). The sensitivity, specificity, positive predictive value, and negative predictive value of microscale endometrial sampling biopsy were 91.7%, 100.0%, 100.0%, and 99.3% for endometrial cancer screening, respectively, and 82.0%, 100.0%, 100.0%, and 99.4% for atypical hyperplasia screening. The medical cost of endometrial sampling biopsy was only 22.1% of the cost of hysteroscopic biopsy. CONCLUSIONS: Microscale endometrial sampling biopsy is a minimally invasive alternative technique for obtaining adequate endometrial specimens for histopathological examination. It has the potential to be used in detecting endometrial cancer and atypical hyperplasia with high efficiency and low cost.

6.
Ther Drug Monit ; 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-33009291

RESUMO

PURPOSE: With the development of industrialization in human society, ambient pollutants are becoming more harmful to human health. Epidemiological and toxicological studies indicate that a close relationship exists between particulate matter with a diameter ≤ 2.5 µm (PM2.5) and neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). To further confirm the relationship, we focus on possible relevant mechanisms of oxidative stress and neuroinflammation underlying the association between PM2.5 and neurodegenerative diseases in the review. METHODS: A literature search was performed on the studies about PM2.5 and neurodegenerative diseases via Pubmed. A total of 113 articles published were selected, and 31 studies were included. RESULTS: PM2.5 can enter the CNS through two main pathways, the BBB and olfactory neurons. The inflammatory response and oxidative stress are two primary mechanisms via which PM2.5 leads to toxicity in the brain. PM2.5 abnormally activates microglia, inducing the neuroinflammatory process. Inflammatory markers such as IL-1ß play an essential role in neurodegenerative diseases such as AD and PD. Moreover, the association between lipid mechanism disorders related to PM2.5 and neurodegenerative diseases has been gaining momentum. CONCLUSION: In conclusion, PM2.5 could significantly increase the risk of neurological disorders, such as AD and PD. Furthermore, any policy aimed at reducing air-polluting emissions and increasing air quality would be protective in human beings.

7.
Injury ; 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-33023742

RESUMO

PURPOSE: To repair multiple skin soft tissue defects of one finger is a challenge to hand surgeons. We introduce a method which can be used to repair multiple skin soft tissue defects of one finger with bilateral flaps in parallel pattern flap based on the dorsal branches of the proper digital artery. METHOD: A patient suffered electric injury in her left index finger with two soft tissue defects, and the areas were 1.6 cm × 1.0 cm and 2.2 cm × 1.2 cm, respectively. And who underwent a homodigital parallel flaps based on the dorsal branches of the proper digital artery to repair in January 2018. The donor sites were covered by full-thickness skin grafting. RESULTS: The flaps and the skin grafting survived uneventfully. All incisions achieved primary healing. The follow-up was 19 months, and the shape of the flaps was satisfactory with soft texture and suitable appearance. TAM of the injured finger was 210°, the level was excellent. The score of VAS was 9. CONCLUSION: The homodigital bilateral flaps in parallel pattern based on the dorsal branches of the proper digital artery are a potential treatment in one-stage for multiple skin soft tissue defects of one finger with reliable blood supply, satisfactory results and simple surgical procedure.

8.
Neurology ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024025

RESUMO

OBJECTIVE: To investigate the spatial patterns and the probable sequences of grey matter atrophy in spinocerebellar ataxia type 3 (SCA3). METHODS: A total of 47 patients with SCA3 and 49 age- and sex-matched healthy control subjects participated in the study. High-resolution T1-weighted magnetic resonance images were examined in all participants. We used the causal network of structural covariance (CasCN) to identify the sequence of grey matter atrophy patterns. This was achieved by applying Granger causality analysis to a grey matter atrophy staging scheme performed by voxel-based morphometry from the network level. RESULTS: Participants in the premanifest stage of the disease showed the presence of focal grey matter atrophy in the vermis. As the disease duration increased, there was progressive grey matter atrophy in the cerebellar, the neostriatum, the frontal lobe, and the parietal lobe. The patients with SCA3 also showed proximal and distal cortical atrophy sequences exerting from the vermis to the regions mainly located in the cerebellum-neostriatum-cortical network. CONCLUSION: Our results, although preliminary in nature, indicate that the grey matter atrophy in SCA3 lies and extends to involve more regions according to distinct anatomical patterns, mainly in the cerebellum-neostriatum-cortical network. These findings advance our understanding on the natural history of structural damage in SCA3, while confirming known clinical features. This could provide unique insight into the ordered sequential process of regional brain atrophy that targets a particular network.

9.
Nanoscale ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026022

RESUMO

Al alloys have widespread industrial applications. However, their mechanical strength is often much lower than steels. Here, we investigate the influence of solutes on achieving ultrahigh strength and thermal stability of nanotwinned Al alloys. In situ micropillar compression tests show the addition of a small amount of Ti can significantly increase the mechanical strength of Al-Ni alloys to 2 GPa. Deformation induced detwinning, Ni segregation and grain coarsening as discovered in binary Al-Ni alloys are mostly absent in the ternary Al-Ni-Ti alloys. Moreover, the ternary Al-Ni-Ti alloys have outstanding thermal stability. Density function theory calculations reveal the synergetic pinning effect of Ni-Ti solute pairs on incoherent twin boundaries. This study demonstrates that the proper selection of synergistic solute pairs is critical to improve the thermal stability and mechanical properties of nanotwinned Al alloys.

10.
Cell Cycle ; : 1-14, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33017570

RESUMO

The poor prognosis of late gastric carcinomas (GC) underscores the necessity to identify novel biomarkers for earlier diagnosis and effective therapeutic targets. MiRNA-324-5p has been shown to be over-expressed in GC, however the biological function of miRNA-324-5p implicated in gastric cancer and its downstream targets were not well understood. Wnt/ß-catenin signaling pathway is aberrantly regulated in GC. We sought to explore if miRNA-324-5p promotes oncogenesis through modulating Wnt signaling and EMT. MiRNA-324-5p is highly expressed in GC based on qRT-PCR and TCGA data. In addition, in vitro cell proliferation, cell migration assays and in vivo animal exenograft were executed to show that miRNA-324-5p is an oncogenic miRNA in GC. MiRNA-324-5p activates Wnt signaling and induces EMT in GC. Further, SUFU was identified as a target of miRNA-324-5p confirmed by western blotting and luciferase assays. Spearson analysis and TCGA data indicate that the expression of SUFU is negatively associated with the expression of miRNA-324-5p. Rescue experiments were performed to determine if SUFU mediates the Wnt activation, EMT and oncogenic function of miRNA-324-5p. MiRNA-324-5p inhibitors plus SUFU siRNAs rescue partially the inhibitory effect on Wnt signaling and EMT caused by miRNA-324-5p inhibitors. Finally, the suppression of cell proliferation, migration, and colony formation ability induced by miRNA-324-5p inhibitors is alleviated by addition of SUFU siRNAs. In summary, miRNA-324-5p is overexpressed in vivo and exerts cell growth and migration-promoting effects through activating Wnt signaling and EMT by targeting SUFU in GC. It represents a potential miRNA with an oncogenic role in human gastric cancer.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33017806

RESUMO

We investigate the radiation of energy and angular momentum from 2D topological systems with broken inversion symmetry and time reversal symmetry. A general theory of far-field radiation is developed using the linear response of 2D materials to the thermal fluctuation of electric currents. Applying the theory to the Haldane model, we verify that the heat radiation complies with Planck's law only at low temperature and deviates from it as temperature becomes high. In contrast to normal metals, angular momentum radiation is possible for this system and exhibits saturation as temperature increases. Parameters crucial to the radiation are investigated and optimized. This research enlightens the possibility of transposing the quantum information to the angular momentum degree of freedom.

12.
Can J Diabetes ; 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-33011132

RESUMO

OBJECTIVES: Copy-number variations (CNVs) are large-scale deletions or duplications of DNA that have required specialized detection methods, such as microarray-based genomic hybridization or multiplex ligation probe amplification. However, recent advances in bioinformatics have made it possible to detect CNVs from next-generation DNA sequencing (NGS) data. Maturity-onset diabetes of the young (MODY) 5 is a subtype of autosomal-dominant diabetes that is often caused by heterozygous deletions involving the HNF1B gene on chromosome 17q12. We evaluated the utility of bioinformatic processing of raw NGS data to detect chromosome 17q12 deletions in MODY5 patients. METHODS: NGS data from 57 patients clinically suspected to have MODY but who were negative for pathogenic mutations using a targeted panel were re-examined using a CNV calling tool (CNV Caller, VarSeq version 1.4.3). Potential CNVs for MODY5 were then confirmed using whole-exome sequencing, cytogenetic analysis and breakpoint analysis when possible. RESULTS: Whole-gene deletions in HNF1B, ranging from 1.46 to 1.85 million basepairs in size, were detected in 3 individuals with features of MODY5. These were confirmed by independent methods to be part of a more extensive 17q12 deletion syndrome. Two additional patients carrying a 17q12 deletion were subsequently diagnosed using this method. CONCLUSIONS: Large-scale deletions are the most common cause of MODY5 and can be detected directly from NGS data, without the need for additional methods.

13.
Angiogenesis ; 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33011960

RESUMO

Cardiovascular diseases (CVDs) are the leading causes of death worldwide. Increasing reports demonstrated that non-coding RNAs (ncRNAs) have been crucially involved in the development of CVDs. Piwi-interacting RNAs (piRNAs) are a novel cluster of small non-coding RNAs with strong uracil bias at the 5' end and 2'-O-methylation at the 3' end that are mainly present in the mammalian reproductive system and stem cells and serve as potential modulators of developmental and pathophysiological processes. Recently, piRNAs have been reported to be widely expressed in human tissues and can potentially regulate various diseases. Specifically, concomitant with the development of next-generation sequencing techniques, piRNAs have been found to be differentially expressed in CVDs, indicating their potential involvement in the occurrence and progression of heart diseases. However, the molecular mechanisms and signaling pathways involved with piRNA function have not been fully elucidated. In this review, we present the current understanding of the piRNAs from the perspectives of biogenesis, characteristics, biological function, and regulatory mechanisms, and highlight their potential roles and underlying mechanisms in CVDs, which will provide new insights into the potential applications of piRNAs in the clinical diagnosis, prognosis, and therapeutic strategies for heart diseases.

14.
Biosci Rep ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33015714

RESUMO

Allergic Rhinitis (AR) is a non-infectious chronic inflammatory disease of nasal mucosa provoking Th17 response. Chlorogenic acid (CGA), one of the most abundant polyphenol compounds in various agricultural products, possess anti-viral, anti-inflammatory, and anti-bacterial properties. However, the effect of CGA on AR is unclear. Thus, our study explored the effect of CGA in modulating AR-related symptoms and immunoreaction especially Th17 response. AR mice were induced by ovalbumin (OVA) administration and further treated with CGA or dexamethasone. The frequencies of rubbing and sneezing of AR mice were recorded. Histopathological of nasal mucosa were conducted by hematoxylin-eosin staining and periodic acid-schiff staining. The serum and nasal mucosa levels of OVA-immunoglobulin (Ig)E, interferon (IFN)-γ, retinoic acid-associated nuclear orphan receptor (ROR)-γt, and interleukin (IL)-17A were measured by enzyme-linked immunosorbent assay, qRT-PCR, or western blot. The ratio of CD4+IL-17+Th17 cells to CD4+T cells in peripheral blood of AR mice was assessed by flow cytometer. CGA diminished the frequencies of rubbing and sneezing of AR mice in a concentration-dependent manner. CGA attenuated histopathological abnormalities and decreased goblet cell number in nasal mucosal of AR mice. CGA decreased the serum levels of OVA-IgE, ROR-γt, and IL-17A, while increasing the serum level of IFN-γ in AR mice. Meanwhile, CGA decreased the ratio of CD4+IL-17+Th17 cells to CD4+T cells in peripheral blood and the mRNA and protein levels of IL-17A and ROR-γt in AR mice. CGA ameliorated AR-related symptoms in mice by regulating Th17 cells, which could be a candidate for the treatment of AR.

15.
Insects ; 11(10)2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33036463

RESUMO

Mitochondrial DNA sequences can be transferred into the nuclear genome, giving rise to nuclear mitochondrial DNA sequences (NUMTs). NUMTs have been described in numerous eukaryotes. However, the studies on the distribution of NUMTs and its influencing factors are still inadequate and even controversial. Previous studies have suggested that Hymenoptera may be a group rich in NUMTs, in which we selected 11 species of fig wasps (Chalcidoidea, Hymenoptera) to analyze the distribution and evolution of NUMTs at the genomic level. The results showed that the contents of NUMTs varied greatly in these species, and bursts of NUMTs existed in some species or lineages. Further detailed analyses showed that the large number of NUMTs might be related to the large genomes; NUMTs tended to be inserted into unstable regions of the genomes; and the inserted NUMTs might also be affected by transposable elements (TEs) in the neighbors, leading to fragmentations and duplications, followed by bursts of NUMTs. In summary, our results suggest that a variety of genomic environmental factors can determine the insertion and post-insertion fate of NUMTs, resulting in their species- or lineage-specific distribution patterns, and that studying the evolution of NUMTs can provide good evidence and theoretical basis for exploring the dynamics of exogenous DNA entering into the nuclear genome.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33037752

RESUMO

Pickering emulsions have been shown to be an excellent platform for interfacial catalysis. However, developing simple and efficient strategies to achieve the goal of product separation and catalyst and emulsifier recovery is still a challenge. Herein, we report for the first time the switchable transition between emulsification and demulsification triggered by UV and visible light in a novel class of light-responsive Pickering emulsions fabricated from Pd supported silica nanoparticles, azobenzene ionic liquid surfactant, n-octane and water. It is shown that light-switchable emulsification and demulsification of the Pickering emulsions is attributed to the adsorption of azobenzene ionic liquid surfactant on the surface of the nanoparticles and the light switched surface activity of the ionic liquid surfactant. This feature enables the Pickering emulsion to be used as an easily controlled micro-reactor with the functions of catalytic reaction, product separation as well as emulsifier and catalyst recycling. As an example, highly efficient catalytic hydrogenation of some unsaturated hydrocarbons at room temperature and atmospheric pressure has been performed in this system, with product separation and emulsifier and catalyst re-use achievable in a simple way.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33037783

RESUMO

OBJECTIVE: The objective of this study was to identify a sample of youth in distinct stages of risk for the development of a serious mental illness (SMI) according to a published clinical staging model and to follow this sample longitudinally to determine clinical changes over time. This article reports the 6- and 12-month follow-up of the cohort. METHODS: This study recruited 243 youth, ages 12 to 25. The sample included (a) 42 healthy controls, (b) 41 nonhelpseeking individuals with no mental illness but some risk of SMI, for example, having a first-degree relative with an SMI (stage 0), (c) 53 youth experiencing distress and mild symptoms of anxiety or depression (stage 1a), and (d) 107 youth with attenuated symptoms of SMIs such as bipolar disorder or psychosis (stage 1b). Participants completed a range of measures assessing depression, anxiety, mania, suicide ideation, attenuated psychotic symptoms, negative symptoms, anhedonia and beliefs about oneself at baseline, 6- and 12-months. RESULTS: There were few changes for healthy controls and stage 0 participants, although approximately 7% did move to a symptomatic stage within 12-months. Of stage 1a participants, 50% remained symptomatic, with 7.5% moving to stage 1b or developing a SMI. Approximately 9% of stage 1byouth developed a SMI within 12-months and approximately one-third had remission of symptoms during the follow-up. CONCLUSIONS: Results suggest that the implementation of a transdiagnostic staging model may be useful in youth mental health and support consideration of clinical stage-based treatment for youth with early features of risk.

18.
BMC Pregnancy Childbirth ; 20(1): 603, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33032551

RESUMO

INTRODUCTION: Low birthweight (LBW) is a significant public health issue, and maternal smoking is the most prevalent preventable cause of LBW. But there is limited evidence on association of LBW among children and cigarette smoke exposure in mothers in China. In this cross-sectional study, we try to explore if the LBW in children is positively associated with mothers' prenatal cigarette smoke exposure. METHODS: We selected 8, 586 mothers and their singleton children in 2018 in Songjiang district, Shanghai. Birthweight of children and gestational weeks of mother was identified by birth records in the hospital, we classified mothers' prenatal cigarette smoke status into the first-hand smoke (FHS) exposure and the second-hand smoke (SHS) exposure. We use SAS 9.1.3 software to calculate the prevalence of children's LBW and the prevalence of mothers' prenatal cigarette smoke exposure including FHS and SHS. Chi-square test and logistic regression were used to analyze the difference. RESULTS: In 8, 586 women, The prenatal FHS and SHS exposure prevalence was 0.9 and 20.8%, respectively. The mean birthweight of children was 3315.5 g with a standard deviation of 497.2 g, the mean birthweight was 167.7 g and 66.1 g lower in children born to mothers with prenatally FHS and SHS exposure compared with those children whose mother were not exposed, respectively. The children's LBW prevalence was 4.7% in this study. By comparing with children whose mother were not exposed, the LBW prevalence was higher among children whose mother were prenatally exposed to FHS [OR (Odds Ratios) = 2.91, 95% confidence interval (CI) (1.49, 5.68)], and SHS [OR = 2.35, 95% CI (1.90, 2.89)]. CONCLUSIONS: Children's LBW is positively associated with mothers' prenatal tobacco smoke exposure both for FHS and SHS. So implementing tobacco control measures is crucial to lower smoking prevalence among women, and decrease smoking prevalence of their family members as well as work fellows.

19.
Biosens Bioelectron ; 169: 112655, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33007614

RESUMO

Benefit from the efficient energy transfer, aggregation-induced emission (AIE) and host-guest recognition as strategies of signal amplification and specific binding have been applied to establish the sensing system; however, the application of these two attractive strategies in one system is rare. Herein, we propose a "turn-on" to "turn-off" fluorescent strategy for sensitive detection of ß-galactosidase (ß-Gal) based on the application of AIE and host-guest recognition. In this work, a novel red-emitted (635 nm) copper nanoclusters (CuNCs) protected by dithioerythritol (DTE) and ß-cyclodextrin (ß-CD) has been found to possess AIE property induced by aluminum cations to achieve the "turn-on" process, and the coordinated behavior between aluminum cations and DTE/ß-CD CuNCs is also discussed. As the hydrolysis product of ß-Gal and 4-nitrophenyl-ß-D-galactopyranoside, p-nitrophenol can combine with ß-CD in DTE/ß-CD CuNCs by the host-guest recognition to realize the efficient photoelectron transfer to "turn-off" the fluorescence. This strategy performs the exciting linear range of 0.0-50.0 U/L and detection limit of 0.56 U/L (S/N = 3) for sensitive detection of ß-Gal and further applies in biologic samples successfully. As far as we know, this is the first work to combine AIE and host-guest recognition in one system to construct the sensing platform, which can achieve efficient and specific energy transfer to improve the sensitivity of the system.

20.
J Mol Cell Cardiol ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33045251

RESUMO

AIMS: Calcific aortic valve disease (CAVD) is a primary cause of cardiovascular mortality; however, its mechanisms are unknown. Currently, no effective pharmacotherapy is available for CAVD. Aldo-keto reductase family 1 member B (Akr1B1) has been identified as a potential therapeutic target for valve interstitial cell calcification. Herein, we hypothesized that inhibition of Akr1B1 can attenuate aortic valve calcification. METHODS AND RESULTS: Normal and degenerative tricuspid calcific valves from human samples were analyzed by immunoblotting and immunohistochemistry. The results showed significant upregulation of Akr1B1 in CAVD leaflets. Akr1B1 inhibition attenuated calcification of aortic valve interstitial cells in osteogenic medium. In contrast, overexpression of Akr1B1 aggravated calcification in osteogenic medium. Mechanistically, using RNA sequencing (RNAseq), we revealed that Hippo-YAP signaling functions downstream of Akr1B1. Furthermore, we established that the protein level of the Hippo-YAP signaling effector active-YAP had a positive correlation with Akr1B1. Suppression of YAP reversed Akr1B1 overexpression-induced Runx2 upregulation. Moreover, YAP activated the Runx2 promoter through TEAD1 in a manner mediated by ChIP and luciferase reporter systems. Animal experiments showed that the Akr1B1 inhibitor epalrestat attenuated aortic valve calcification induced by a Western diet in LDLR-/- mice. CONCLUSION: This study demonstrates that inhibition of Akr1B1 can attenuate the degree of calcification both in vitro and in vivo. The Akr1B1 inhibitor epalrestat may be a potential treatment option for CAVD.

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