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While immune checkpoint blockade (ICB) has shown promise for clinical cancer therapy, its efficacy has only been observed in a limited subset of patients and the underlying mechanisms regulating innate and acquired resistance to ICB of tumor cells remain poorly understood. Here, we identified ependymin-related protein 1 (EPDR1) as an important tumor-intrinsic regulator of PD-L1 expression and tumor immune evasion. Aberrant expression of EPDR1 in hepatocellular carcinoma is associated with immunosuppression. Mechanistically, EPDR1 binds to E3 ligase TRIM21 and disrupts its interaction with IkappaB kinase-b, suppressing its ubiquitylation and autophagosomal degradation and enhancing NF-κB-mediated transcriptional activation of PD-L1. Further, we validated through a mouse liver cancer model that EPDR1 mediates exhaustion of CD8+ T cells and promotes tumor progression. In addition, we observed a positive correlation between EPDR1 and PD-L1 expression in both human and mouse liver cancer samples. Collectively, our study reveals a previously unappreciated role of EPDR1 in orchestrating tumor immune evasion and cancer progression.
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Optical vortices with spin and orbital angular momentum (SAM and OAM) states offer multiple degrees of freedom for manipulating optical fields and thus enable great potentials in optical information processing. Recently, the optical metasurface has become an important platform for vortex beam generation and steering. However, the strong spin-orbit interaction on such metasurfaces usually leads to spin locked OAM generation, which limits the complete control of the angular momentum state of light. Here, we propose to solve this constraint using geometric phase controlled nonlinear chiroptical metasurfaces. The metasurface consists of two types of plasmonic meta-atoms which have opposite handedness and exhibit a strong spin-dependent circular dichroism effect. By encoding specific phase singularities and phase gradients to different channels, we experimentally demonstrate the spin unlocked second harmonic beam steering. The proposed nonlinear chiroptical metasurfaces may have important applications in developing multifunctional nonlinear optical devices.
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The ability to manipulate magnetic states by a low electric current represents a fundamental desire in spintronics. In recent years, two-dimensional van der Waals (vdW) magnetic materials have attracted an extensive amount of attention due to their appreciable spin-orbit torque effect. However, for most known vdW ferromagnets, their relatively low Curie temperatures (TC) limit their applications. Consequently, low-power vdW spintronic devices that can operate at room temperature are in great demand. In this research, we fabricate nanodevices based on a solitary thin flake of vdW ferromagnet Fe3GaTe2, in which we successfully achieve nonvolatile and highly efficient magnetization switching by small currents at room temperature. Notably, the switching current density and the switching power dissipation are as low as 1.7 × 105 A/cm2 and 1.6 × 1013 W/m3, respectively, with an external magnetic field of 80 Oe; both are much reduced compared to those of conventional magnet/heavy metal heterostructure devices and other vdW devices.
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Recently, van der Waals (vdW) antiferromagnets have been proposed to be crucial for spintronics due to their favorable properties compared to ferromagnets, including robustness against magnetic perturbation and high frequencies of spin dynamics. High-performance and energy-efficient spin functionalities often depend on the current-driven manipulation and detection of spin states, highlighting the significance of two-dimensional metallic antiferromagnets, which have not been much explored due to the lack of suitable materials. Here, we report a new metallic vdW antiferromagnet obtained from the ferromagnet Fe3GaTe2 by cobalt (Co) doping. Through the layer-number-dependent Hall resistance and magnetoresistance measurements, an evident odd-even layer-number effect has been observed in its few-layered flakes, suggesting that it could host an A-type antiferromagnetic structure. This peculiar layer-number-dependent magnetism in Co-doped Fe3GaTe2 helps unravel the complex magnetic structures in such doped vdW magnets, and our finding will enrich material candidates and spin functionalities for spintronic applications.
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OBJECTIVE: Comparing the effects of extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) on outcomes in patients with in-hospital cardiac arrest (IHCA) in China. The benefits of ECPR over CCPR in patients with IHCA remain controversial. DESIGN: This article analyzed data from the BASeline Investigation of In-hospital Cardiac Arrest (BASIC-IHCA) study, which consecutively enrolled patients with IHCA from July 1, 2019, to December 31, 2020. Patients who received ECPR were selected as the case group and matched with patients who received CCPR as the control group by propensity score at a ratio of 1:4. A parallel questionnaire survey of participating hospitals was conducted, to collect data on ECPR cases from January 1, 2021 to November 30, 2021. The primary outcome was survival to discharge or 30-day survival. SETTING: We included 39 hospitals across 31 provinces in China. PATIENTS: Patients receiving cardiopulmonary resuscitation and without contraindications to ECPR were selected from the BASIC-IHCA database. Patients older than 75 years, not witnessed, or with cardiopulmonary resuscitation duration less than 10 min were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 4853 patients met the inclusion criteria before matching, with 34 undergoing ECPR (median age, 56.5 yr; 67.65% male) and 4819 underwent CCPR (median age, 59 yr; 64.52% male). There were 132 patients receiving CCPR and 33 patients receiving ECPR who were eventually matched. The ECPR group had significantly higher survival rates at discharge or 30-day survival (21.21% vs. 7.58%, p = 0.048). The ECPR group had significantly lower mortality rates (hazard ratio 0.57; 95% CI, 0.38-0.91) than the CCPR group at discharge or 30 days. Besides the BASIC-IHCA study, the volume of ECPR implementations and the survival rate of patients with ECPR (29.4% vs. 10.4%. p = 0.004) in participating hospitals significantly improved. CONCLUSIONS: ECPR may be beneficial compared with CCPR for patient survival after IHCA and should be considered for eligible patients with IHCA.
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Reanimação Cardiopulmonar , Oxigenação por Membrana Extracorpórea , Parada Cardíaca , Pontuação de Propensão , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Reanimação Cardiopulmonar/métodos , Parada Cardíaca/terapia , Parada Cardíaca/mortalidade , Oxigenação por Membrana Extracorpórea/métodos , Oxigenação por Membrana Extracorpórea/mortalidade , China/epidemiologia , Idoso , Estudos de Coortes , Adulto , Mortalidade HospitalarRESUMO
Complex biomedical data generated during clinical, omics and mechanism-based experiments have increasingly been exploited through cloud- and visualization-based data mining techniques. However, the scientific community still lacks an easy-to-use web service for the comprehensive visualization of biomedical data, particularly high-quality and publication-ready graphics that allow easy scaling and updatability according to user demands. Therefore, we propose a community-driven modern web service, Hiplot (https://hiplot.org), with concise and top-quality data visualization applications for the life sciences and biomedical fields. This web service permits users to conveniently and interactively complete a few specialized visualization tasks that previously could only be conducted by senior bioinformatics or biostatistics researchers. It covers most of the daily demands of biomedical researchers with its equipped 240+ biomedical data visualization functions, involving basic statistics, multi-omics, regression, clustering, dimensional reduction, meta-analysis, survival analysis, risk modelling, etc. Moreover, to improve the efficiency in use and development of plugins, we introduced some core advantages on the client-/server-side of the website, such as spreadsheet-based data importing, cross-platform command-line controller (Hctl), multi-user plumber workers, JavaScript Object Notation-based plugin system, easy data/parameters, results and errors reproduction and real-time updates mode. Meanwhile, using demo/real data sets and benchmark tests, we explored statistical parameters, cancer genomic landscapes, disease risk factors and the performance of website based on selected native plugins. The statistics of visits and user numbers could further reflect the potential impact of this web service on relevant fields. Thus, researchers devoted to life and data sciences would benefit from this emerging and free web service.
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Software , Interface Usuário-Computador , Biologia Computacional/métodos , Visualização de Dados , Genômica , HumanosRESUMO
OBJECTIVE: To explore the factors influencing C-reactive protein (CRP) status in neonates on admission after birth. METHODS: 820 newborns born and hospitalized at Xiangya Hospital of Central South University from Jan. 2020 to Dec. 2020 were retrospectively analyzed. Maternal medical history and medication use during pregnancy, neonatal demographic information and status at birth were collected through the electronic medical record system. Statistical software was used to analyze the possible relationship between perinatal factors and CRP on admission after birth. RESULTS: A total of 820 neonates were analyzed, including 463 males and 357 females with a mean gestational age (GA) of 36.07 ± 3.30 weeks. (1) Multifactor Logistic regression analysis: larger GA (OR: 1.13, 95%CI: 1.00-1.28, P = 0.042), premature rupture of membranes (PROM) ≥ 18 h (OR: 2.39, 95%CI: 1.35-4.23, P = 0.003) and maternal autoimmune diseases (OR: 5.30, 95%CI: 2.15-13.07, P < 0.001) were independent risk factors for CRP ≥ 8 mg/L. Cesarean delivery (OR 0.40, 95%CI: 0.26-0.60, P < 0.001) was independent protective factor for CRP ≥ 8 mg/L. (2) Threshold effect analysis: A non-linear relationship was found between GA and CRP. When GA is less than 33.9 weeks, the risk of CRP ≥ 8 mg/L was reduced by 28% with one week increased (P < 0.001), and when GA is more than 33.9 weeks, the risk of CRP ≥ 8 mg/L was increased by 61% with one week increased (P < 0.001). CONCLUSIONS: GA, PROM, maternal autoimmune diseases and cesarean delivery were all independent influences neonatal CRP ≥ 8 mg/L on admission, and there was a nonlinear relationship between GA and neonatal CRP ≥ 8 mg/L on admission.
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Doenças Autoimunes , Doenças do Recém-Nascido , Nascimento Prematuro , Gravidez , Masculino , Feminino , Recém-Nascido , Humanos , Lactente , Proteína C-Reativa/análise , Estudos Retrospectivos , Idade GestacionalRESUMO
BACKGROUND: To investigate the association between sex and neonatal respiratory distress syndrome (NRDS). METHODS: Neonates born at our hospital and transferred to the neonatal department within 1 h were retrospectively analyzed. Depending on whether they developed NRDS during their hospital stay, the neonates was divided into NRDS and non-NRDS groups. There were 142 neonates in the NRDS group (95 males and 47 females) and 310 neonates in the non-NRDS group (180 males and 140 females). The neonates' data on gestational age (GA), sex, birth weight, white blood cell count (WBC), platelet count (PLT), C-reactive protein (CRP), total immunoglobulin M (total IgM), gestational diabetes mellitus(GDM), antenatal steroids use, meconium-stained amniotic fluid, and preterm premature rupture of membranes(PPROM) were gathered. RESULTS: 452 neonates (265 males and 187 females) were involved for the purpose of collecting basic characteristic. Multivariate analysis, males had a 1.87 times higher risk of NRDS than females (P < 0.05) after controlling for the confounding effects of GA, birth weight, WBC, PLT, CRP, total IgM, GDM, antenatal steroids use, meconium-stained amniotic fluid, and PPROM. CONCLUSIONS: Sex was associated with NRDS; males had a considerably higher risk of NRDS than females.
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Ruptura Prematura de Membranas Fetais , Doenças do Recém-Nascido , Complicações na Gravidez , Síndrome do Desconforto Respiratório do Recém-Nascido , Recém-Nascido , Masculino , Gravidez , Humanos , Feminino , Peso ao Nascer , Estudos Retrospectivos , Esteroides , Imunoglobulina MRESUMO
In order to minimize the disparity between visible and infrared modalities and enhance pedestrian feature representation, a cross-modality person re-identification method is proposed, which integrates modality generation and feature enhancement. Specifically, a lightweight network is used for dimension reduction and augmentation of visible images, and intermediate modalities are generated to bridge the gap between visible images and infrared images. The Convolutional Block Attention Module is embedded into the ResNet50 backbone network to selectively emphasize key features sequentially from both channel and spatial dimensions. Additionally, the Gradient Centralization algorithm is introduced into the Stochastic Gradient Descent optimizer to accelerate convergence speed and improve generalization capability of the network model. Experimental results on SYSU-MM01 and RegDB datasets demonstrate that our improved network model achieves significant performance gains, with an increase in Rank-1 accuracy of 7.12% and 6.34%, as well as an improvement in mAP of 4.00% and 6.05%, respectively.
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To address challenges related to the inadequate representation and inaccurate discrimination of pedestrian attributes, we propose a novel method for person re-identification, which leverages global feature learning and classification optimization. Specifically, this approach integrates a Normalization-based Channel Attention Module into the fundamental ResNet50 backbone, utilizing a scaling factor to prioritize and enhance key pedestrian feature information. Furthermore, dynamic activation functions are employed to adaptively modulate the parameters of ReLU based on the input convolutional feature maps, thereby bolstering the nonlinear expression capabilities of the network model. By incorporating Arcface loss into the cross-entropy loss, the supervised model is trained to learn pedestrian features that exhibit significant inter-class variance while maintaining tight intra-class coherence. The evaluation of the enhanced model on two popular datasets, Market1501 and DukeMTMC-ReID, reveals improvements in Rank-1 accuracy by 1.28% and 1.4%, respectively, along with corresponding gains in the mean average precision (mAP) of 1.93% and 1.84%. These findings indicate that the proposed model is capable of extracting more robust pedestrian features, enhancing feature discriminability, and ultimately achieving superior recognition accuracy.
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SUMMARY: UCSC Xena platform provides huge amounts of processed cancer omics data from large cancer research projects (e.g. TCGA, CCLE and PCAWG) or individual research groups and enables unprecedented research opportunities. However, a graphical user interface-based tool for interactively analyzing UCSC Xena data and generating elegant plots is still lacking, especially for cancer researchers and clinicians with limited programming experience. Here, we present UCSCXenaShiny, an R Shiny package for quickly searching, downloading, exploring, analyzing and visualizing data from UCSC Xena data hubs. This tool could effectively promote the practical use of public data, and can serve as an important complement to the current Xena genomics explorer. AVAILABILITY AND IMPLEMENTATION: UCSCXenaShiny is an open source R package under GPLv3 license and it is freely available at https://github.com/openbiox/UCSCXenaShiny or https://cran.r-project.org/package=UCSCXenaShiny. The docker image is available at https://hub.docker.com/r/shixiangwang/ucscxenashiny. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Neoplasias , Software , Humanos , Genômica , Interpretação Estatística de DadosRESUMO
High-altitude cardiac injury (HACI) is one of the common tissue injuries caused by high-altitude hypoxia that may be life threatening. Notoginsenoside R1 (NG-R1), a major saponin of Panax notoginseng, exerts anti-oxidative, anti-inflammatory, and anti-apoptosis effects, protecting the myocardium from hypoxic injury. This study aimed to investigate the protective effect and molecular mechanism of NG-R1 against HACI. We simulated a 6000 m environment for 48 h in a hypobaric chamber to create a HACI rat model. Rats were pretreated with NG-R1 (50, 100 mg/kg) or dexamethasone (4 mg/kg) for 3 days and then placed in the chamber for 48 h. The effect of NG-R1 was evaluated by changes in Electrocardiogram parameters, histopathology, cardiac biomarkers, oxidative stress and inflammatory indicators, key protein expression, and immunofluorescence. U0126 was used to verify whether the anti-apoptotic effect of NG-R1 was related to the activation of ERK pathway. Pretreatment with NG-R1 can improve abnormal cardiac electrical conduction and alleviate high-altitude-induced tachycardia. Similar to dexamethasone, NG-R1 can improve pathological damage, reduce the levels of cardiac injury biomarkers, oxidative stress, and inflammatory indicators, and down-regulate the expression of hypoxia-related proteins HIF-1α and VEGF. In addition, NG-R1 reduced cardiomyocyte apoptosis by down-regulating the expression of apoptotic proteins Bax, cleaved caspase 3, cleaved caspase 9, and cleaved PARP1 and up-regulating the expression of anti-apoptotic protein Bcl-2 through activating the ERK1/2-P90RSK-Bad pathway. In conclusion, NG-R1 prevented HACI and suppressed apoptosis via activation of the ERK1/2-P90RSK-Bad pathway, indicating that NG-R1 has therapeutic potential to treat HACI.
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Realization of ferromagnetism in the two-dimensional (2D) van der Waals (vdW) crystals opens up a vital route to understand the magnetic ordering in the 2D limit and to design novel spintronics. Here, we report enriched layer-number-dependent magnetotransport properties in the vdW ferromagnet Fe5GeTe2. By studying the magnetoresistance and anomalous Hall effect (AHE) in nanoflakes with thicknesses down to monolayer, we demonstrate that while the bulk crystals exhibit soft ferromagnetism with an in-plane magnetic anisotropy, hard ferromagnetism develops upon thinning, and a perpendicular easy-axis anisotropy is realized in bilayer flakes, which is accompanied by a pronounced enhancement of AHE because of extrinsic mechanisms. For the monolayer flakes, the hard ferromagnetism is replaced by spin-glass-like behavior, in accordance with the localization effect in the 2D limit. Our results highlight the thickness-based tunability of the magnetotransport properties in the atomically thin vdW magnets that promises engineering of high-performance spintronic devices.
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Osteosarcoma (OS) is an aggressive tumor with a rare incidence. Extended surgical resections are the prevalent treatment for OS, which may cause critical-size bone defects. These bone defects lead to dysfunction, weakening the post-surgical quality of patients' life. Hence, an ideal therapeutic agent for OS should simultaneously possess anti-cancer and bone repair capacities. Curcumin (CUR) has been reported in OS therapy and bone regeneration. However, it is not clear how CUR suppresses OS development. Conventionally, CUR is considered a natural antioxidant in line with its capacity to promote the nuclear translocation of a nuclear transcription factor, nuclear factor erythroid 2 (NRF2). After nuclear translocation, NRF2 can activate the transcription of some antioxidases, thereby circumventing excess reactive oxygen species (ROS) that are deleterious to cells. Intriguingly, this research demonstrated that, in vitro, 10 and 20 µM CUR increased the intracellular ROS in MG-63 cells, damaged cells' DNA, and finally caused apoptosis of MG-63 cells, although increased NRF2 protein level and the expression of NRF2-regulated antioxidase genes were identified in those two groups.
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Neoplasias Ósseas , Curcumina , Osteossarcoma , Humanos , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Curcumina/uso terapêutico , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Osteossarcoma/tratamento farmacológico , Apoptose , Neoplasias Ósseas/tratamento farmacológicoRESUMO
The present study aimed to investigate the protective effect of S-propargyl-cysteine (SPRC) on atherosclerosis progression in mice. A mouse model of vulnerable atherosclerotic plaque was created in ApoE-/- mice by carotid artery tandem stenosis (TS) combined with a Western diet. Macrophotography, lipid profiles, and inflammatory markers were measured to evaluate the antiatherosclerotic effects of SPRC compared to atorvastatin as a control. Histopathological analysis was performed to assess the plaque stability. To explore the protective mechanism of SPRC, human umbilical vein endothelial cells (HUVECs) were cultured in vitro and challenged with oxidized low-density lipoprotein (ox-LDL). Cell viability was determined with a Cell Counting Kit-8 (CCK-8). Endothelial nitric oxide synthase (eNOS) phosphorylation and mRNA expression were detected by Western blot and RT-qPCR respectively. The results showed that the lesion area quantified by en face photographs of the aortic arch and carotid artery was significantly less, plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were reduced, plaque collagen content was increased and matrix metalloproteinase-9 (MMP-9) was decreased in 80 mg/kg per day SPRC-treated mice compared with model mice. These findings support the role of SPRC in plaque stabilization. In vitro studies revealed that 100 µmol/L SPRC increased the cell viability and the phosphorylation level of eNOS after ox-LDL challenge. These results suggest that SPRC delays the progression of atherosclerosis and enhances plaque stability. The protective effect may be at least partially related to the increased phosphorylation of eNOS in endothelial cells.
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Aterosclerose , Placa Aterosclerótica , Animais , Humanos , Camundongos , Colesterol/metabolismo , Cisteína/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Lipoproteínas LDL/farmacologia , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologiaRESUMO
Energy metabolism is crucial in maintaining cellular homeostasis and adapting to stimuli for tubular cells. However, the underlying mechanisms remain largely unknown. Here, we report that PP2Acα was upregulated in damaged tubular cells from patients and animal models with acute or chronic kidney injury. Using in vitro and in vivo model, we demonstrated that PP2Acα induction in damaged tubular cells suppresses fatty acid oxidation and promotes glycolysis, leading to cell death and fibrosis. Mechanistically, we revealed that PP2Acα dephosphorylates ACC through interaction with B56δ, leading to the regulation of fatty acid oxidation. Furthermore, PP2Acα also dephosphorylates p-Glut1 (Thr478) and suppresses Trim21-mediated Glut1 ubiquitination and degradation, leading to the promotion of glucose intake and glycolysis. Thus, this study adds new insight into the tubular cell metabolic alterations in kidney diseases. PP2Acα may be a promising therapeutic target for kidney injury.
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Glicólise , Rim , Animais , Ácidos Graxos , Transportador de Glucose Tipo 1 , Fosfoproteínas FosfatasesRESUMO
Numerous studies on the bioavailability of graphene-based nanomaterials relate to the water-only exposure route. However, the sediment exposure route should be the most important pathway for benthic organisms to ingest graphene, while to date little work on the bioavailability of graphene in benthic organisms has been explored. In this study, with the help of carbon-14-labeled few-layer graphene (14C-FLG), we quantificationally compared the bioaccumulation, biodistribution, and elimination kinetics of 14C-FLG in loaches via waterborne and sediment exposures. After 72 h of exposure, the accumulated 14C-FLG in loaches exposed via waterborne was 14.28 µg/g (dry mass), which was 3.18 times higher than that (4.49 µg/g) exposed via sediment. The biodistribution results showed that, compared to waterborne exposure, sediment exposure remarkably facilitated the transport of 14C-FLG from the gut into the liver, which made it difficult to be excreted. Although 14C-FLG did not cause significant hepatotoxicity, the disruption of intestinal microbiota homeostasis, immune response, and several key metabolic pathways in the gut were observed, which may be due to the majority of 14C-FLG being accumulated in the gut. Overall, this study reveals the different bioavailabilities of graphene in loaches via waterborne and sediment exposures, which is helpful in predicting its bioaccumulation capability and trophic transfer ability.
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Cipriniformes , Grafite , Poluentes Químicos da Água , Animais , Disponibilidade Biológica , Radioisótopos de Carbono , Cipriniformes/metabolismo , Sedimentos Geológicos , Distribuição Tecidual , Poluentes Químicos da Água/metabolismoRESUMO
INTRODUCTION: Chronic inflammation and tissue remodeling always occur together in chronic rhinosinusitis (CRS). Epithelial-mesenchymal transition (EMT) plays a critical role in airway remodeling. OBJECTIVE: Changes of epithelial cells in sinus mucosa in different subtypes of CRS, especially in eosinophilic chronic rhinosinusitis with nasal polyps, and the role of EMT and eosinophils (EOS) in airway remodeling are still unknown. METHODS: We included 85 patients in this study. They were divided into 4 groups: a normal control (NC) group, a chronic rhinosinusitis without nasal polyps (CRSsNP) group, an eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) group, and a noneosinophilic chronic rhinosinusitis with nasal polyps (non-ECRSwNP) group. Clinical data were all collected and analyzed. Standard hematoxylin and eosin staining, immunohistochemical staining, and 2-color immunofluorescence staining were performed. Biomarkers of EMT, epithelial cadherin, and vimentin were labeled. The immunohistochemistry results of each group were counted and statistically analyzed. RESULTS AND CONCLUSION: E-cadherin was downregulated, and vimentin was upregulated in epithelial tissue from the ECRSwNP group, compared with that from the control group and the other groups. The number of vimentin-expressing epithelial cells correlated with sinus CT imaging Lund-Mackay scores (r = 0.560, p < 0.001). Moreover, expression levels of vimentin in the epithelium were associated with numbers of infiltrating EOS in tissues (r = 0.710, p < 0.001) and the peripheral blood EOS ratio (r = 0.594, p < 0.001). EMT occurred in patients with CRSwNP, especially in those with ECRSwNP. Epithelial reprogramming correlates with eosinophil infiltration and disease severity. Eosinophils contributed to impairment of epithelial function and promoted EMT in CRSwNP.
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Pólipos Nasais , Rinite , Sinusite , Doença Crônica , Eosinófilos/metabolismo , Transição Epitelial-Mesenquimal , Humanos , Pólipos Nasais/complicações , Pólipos Nasais/metabolismo , Rinite/complicações , Rinite/metabolismo , Sinusite/complicações , Sinusite/metabolismoRESUMO
PURPOSE: To evaluate the plaque removal efficacy of a compacted dual-head power toothbrush (DH) in comparison with a single-head power toothbrush (SH). METHODS: 24 healthy university students were included in this split-mouth and single-center clinical trial. The DH and SH were randomly assigned to brush the left/right half mouth in the first visit. Testing time points were 30 and 60 seconds. Additionally, 15 and 45 seconds were set for the DH period. The overall, buccal, lingual, gingival marginal, and proximal plaque scores at different time points were recorded and determined by Rustogi Modification of the Navy Plaque Index. To avoid the influence of the right handedness, subjects were brushed in the second visit after 4 weeks, and the SH and the DH were assigned to the right/left half mouth in an opposite period to that of the first visit. RESULTS: 21 participants completed this study. Overall plaque score reductions of the SH and DH were 29% and 59% (P< 0.05) at 30 seconds, and the reductions were 47% and 77% respectively (P< 0.05) at 60 seconds. Using the DH for 45 seconds reduced significantly more overall, buccal, lingual, and gingival marginal plaque than that of using SH for 60 seconds (P< 0.05). The SH reduced plaque scores significantly less in the right and lower dentitions than left and upper dentitions respectively, while DH reduced comparable plaque scores between these dentitions. The DH is more effective in removing overall, buccal, lingual, gingival marginal, and proximal plaque in healthy university students than the SH, meanwhile DH showed comparable overall plaque reduction rates between different regions of the dentitions. CLINICAL SIGNIFICANCE: This compact dual-head power toothbrush provides a new option to carry out daily plaque control effectively.
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Placa Dentária , Gengivite , Índice de Placa Dentária , Desenho de Equipamento , Humanos , Método Simples-Cego , Escovação Dentária , Resultado do TratamentoRESUMO
Skin wound healing tends to slow down with aging, which is detrimental to both minor wound recovery in daily life and the recovery after surgery. The aim of current study was to explore the effect of histone deacetylase 6 (HDAC6) on wound healing during aging. Cultured human dermal fibroblasts (HDFs) and mouse full-thickness skin wound model were used to explore the functional changes of replicative senescent dermal fibroblasts and the effect of aging on skin wound healing. Scratch wound healing assay revealed significantly decreased migration speed of senescent HDFs, and BrdU incorporation assay indicated their considerably retardant proliferation. The protein expression levels of collagen and HDAC6 were significantly decreased in both senescent HDFs and skin tissues from aged mice. HDAC6 activity inhibition with highly selective inhibitor tubastatin A (TsA) or HDAC6 knockdown with siRNA decreased the migration speed of HDFs and considerably suppressed fibroblast differentiation induced by transforming growth factor-ß1 (TGF-ß1), which suggests the involvement of HDAC6 in regulating fundamental physiological activities of dermal fibroblasts. In vivo full-thickness skin wound healing was significantly delayed in young HDAC6 knockout mice when compared with young wild type mice. In addition, the wound healing was significantly slower in aged wild type mice than that in young wild type mice, and became even worse in aged HDAC6 knockout aged mice. Compared to the aged wild type mice, aged HDAC6 knockout mice exhibited delayed angiogenesis, reduced collagen synthesis, and decreased collagen deposition in skin wounds. Together, these results suggest that delayed skin wound healing in aged mice is associated with impaired fibroblast function. Adequate expression and activity of HDAC6 are required for fibroblasts migration and differentiation.