RESUMO
Diffuse midline gliomas (DMGs) including diffuse intrinsic pontine gliomas (DIPGs) bearing lysine-to-methionine mutations in histone H3 at lysine 27 (H3K27M) are lethal childhood brain cancers. These tumors harbor a global reduction in the transcriptional repressive mark H3K27me3 accompanied by an increase in the transcriptional activation mark H3K27ac. We postulated that H3K27M mutations, in addition to altering H3K27 modifications, reprogram the master chromatin remodeling switch/sucrose nonfermentable (SWI/SNF) complex. The SWI/SNF complex can exist in two main forms termed BAF and PBAF that play central roles in neurodevelopment and cancer. Moreover, BAF antagonizes PRC2, the main enzyme catalyzing H3K27me3. We demonstrate that H3K27M gliomas show increased protein levels of the SWI/SNF complex ATPase subunits SMARCA4 and SMARCA2, and the PBAF component PBRM1. Additionally, knockdown of mutant H3K27M lowered SMARCA4 protein levels. The proteolysis targeting chimera (PROTAC) AU-15330 that simultaneously targets SMARCA4, SMARCA2, and PBRM1 for degradation exhibits cytotoxicity in H3.3K27M but not H3 wild-type cells. AU-15330 lowered chromatin accessibility measured by ATAC-Seq at nonpromoter regions and reduced global H3K27ac levels. Integrated analysis of gene expression, proteomics, and chromatin accessibility in AU-15330-treated cells demonstrated reduction in the levels of FOXO1, a key member of the forkhead family of transcription factors. Moreover, genetic or pharmacologic targeting of FOXO1 resulted in cell death in H3K27M cells. Overall, our results suggest that H3K27M up-regulates SMARCA4 levels and combined targeting of SWI/SNF ATPases in H3.3K27M can serve as a potent therapeutic strategy for these deadly childhood brain tumors.
Assuntos
Neoplasias Encefálicas , Glioma Pontino Intrínseco Difuso , Glioma , Humanos , Criança , Histonas/genética , Adenosina Trifosfatases/metabolismo , Lisina/genética , Cromatina , Glioma/genética , Neoplasias Encefálicas/genética , Mutação , DNA Helicases/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: Biomarkers are biochemical indicators that can identify changes in the structure or function of systems, organs, or cells and can be used to monitor a wide range of biological processes, including cancer. Interleukin-1 receptor antagonist (IL1RA) is an important inflammatory suppressor gene and tumor biomarker. The goal of this study was to investigate the expression of IL1RA, its probable carcinogenic activity, and its diagnostic targets in oral squamous cell carcinoma (OSCC). RESULTS: We discovered that IL1RA was expressed at a low level in OSCC tumor tissues compared to normal epithelial tissues and that the expression declined gradually from epithelial hyperplasia through dysplasia to carcinoma in situ and invasive OSCC. Low IL1RA expression was associated not only with poor survival but also with various clinicopathological markers such as increased infiltration, recurrence, and fatalities. Following cellular phenotyping investigations in OSCC cells overexpressing IL1RA, we discovered that recovering IL1RA expression decreased OSCC cell proliferation, migration, and increased apoptosis. CONCLUSIONS: In summary, our investigation highlighted the possible involvement of low-expression IL1RA in OSCC cells in promoting invasive as well as metastatic and inhibiting apoptosis, as well as the efficacy of IL1RA-focused monitoring in the early detection and treatment of OSCC.
Assuntos
Apoptose , Carcinoma de Células Escamosas , Movimento Celular , Proliferação de Células , Proteína Antagonista do Receptor de Interleucina 1 , Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/genética , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/genética , Movimento Celular/genética , Prognóstico , Masculino , Feminino , Pessoa de Meia-Idade , Linhagem Celular Tumoral , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Idoso , AdultoRESUMO
Fibrotic cataract, including anterior subcapsular cataract (ASC) and posterior capsule opacification, always lead to visual impairment. Epithelial-mesenchymal transition (EMT) is a well-known event that causes phenotypic alterations in lens epithelial cells (LECs) during lens fibrosis. Accumulating studies have demonstrated that microRNAs are important regulators of EMT and fibrosis. However, the evidence explaining how microRNAs modulate the behavior and alter the cellular phenotypes of the lens epithelium in fibrotic cataract is insufficient. In this study, we found that hsa-let-7c-3p is downregulated in LECs in human ASC in vivo as well as in TGFß2-induced EMT in vitro, indicating that hsa-let-7c-3p may participate in modulating the profibrotic processes in the lens. We then demonstrated that overexpression of hsa-let-7c-3p markedly suppressed human LEC proliferation and migration and attenuated TGFß2-induced EMT and injury-induced ASC in a mouse model. In addition, hsa-let-7c-3p mediated lens fibrosis by directly targeting the CDH11 gene, which encodes cadherin-11 protein, an important mediator in the EMT signaling pathway. It decreased cadherin-11 protein expression at the posttranscriptional level but not at the transcriptional level by binding to a specific site in the 3-untranslated region (3'-UTR) of CDH11 mRNA. Moreover, blockade of cadherin-11 expression with a specific short hairpin RNA reversed TGFß2-induced EMT in LECs in vitro. Collectively, these data demonstrated that hsa-let-7c-3p plays a clear role in attenuating ASC development and may be a novel candidate therapeutic for halting fibrosis and maintaining vision.
Assuntos
Caderinas , Opacificação da Cápsula , Catarata , Cristalino , MicroRNAs , Animais , Humanos , Camundongos , Opacificação da Cápsula/genética , Opacificação da Cápsula/metabolismo , Catarata/genética , Catarata/metabolismo , Catarata/patologia , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal , Fibrose , Cristalino/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
Chemokines are small, secreted proteins with chemoattractive properties, which play an important role in the recruitment and activation of immune cells. CXCL11 is a CXC chemokine specific for the CXCR3 receptors, which has been shown to mediate the generation of Th1-type immune responses and have bactericidal effects similar to defensins. Herein, we cloned the full-length cDNA of Chinese soft-shelled turtle (Pelodiscus sinensis) CXCL11, designated as PsCXCL11, which consist of an open reading frame (ORF) of 282 bp encoding 93 amino acids, with estimated molecular weight of 10.055 kDa and isoelectric point of 10.37. The deduced PsCXCL11 sequence had a signal peptide, a highly conserved family-specific small cytokine (SCY) domain, one putative N-glycosylation site and ten potential phosphorylation sites. Phylogenetic analysis showed a close relationship between P. sinensis and Chelydra Serpentina CXCL11. P. sinensis CXCL11 basal expression levels were higher in heart, kidney and spleen than in other organs of health turtles. Infections of Aeromonas hydrophila and Staphylococcus aureus led to significant upregulation of P. sinensis CXCL11 in the blood, while significant upregulation of PsCXCL11 were observed in liver and spleen after infection of A. hydrophila, but not S. aureus. PsCXCL11 recombinant protein with His-tag was successfully expressed by an auto-inducible expression system, and purified by Ni-NTA affinity chromatography. These findings laid a solid foundation for further research towards development of the Chinese soft-shelled turtle as a model for the role of CXCL11 in regulating inflammatory responses to stimulation by invading pathogens.
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Tartarugas , Animais , Tartarugas/genética , Quimiocina CXCL11/genética , Filogenia , Clonagem Molecular , Citocinas/genéticaRESUMO
In the present investigation, a series of dimethoxy or methylenedioxy substituted-cinnamamide derivatives containing tertiary amine moiety (N. N-Dimethyl, N, N-diethyl, Pyrrolidine, Piperidine, Morpholine) were synthesized and evaluated for cholinesterase inhibition and blood-brain barrier (BBB) permeability. Although their chemical structures are similar, their biological activities exhibit diversity. The results showed that all compounds except for those containing morpholine group exhibited moderate to potent acetylcholinesterase inhibition. Preliminary screening of BBB permeability shows that methylenedioxy substituted compounds have better brain permeability than the others. Compound 10c, containing methylenedioxy and pyrrolidine side chain, showed a better acetylcholinesterase inhibition (IC50: 1.52±0.19â µmol/L) and good blood-brain barrier permeability. Further pharmacokinetic investigation of compound 10c using ultra high performance liquid chromatography-mass/mass spectrometry (UPLC-MS/MS) in mice showed that compound 10c in brain tissue reached its peak concentration (857.72±93.56â ng/g) after dosing 30â min. Its half-life in the serum is 331â min (5.52â h), and the CBrain/CSerum at various sampling points is ranged from 1.65 to 4.71(Mean: 2.76) within 24â hours. This investigation provides valuable information on the chemistry and pharmacological diversity of cinnamic acid derivatives and may be beneficial for the discovery of central nervous system drugs.
Assuntos
Barreira Hematoencefálica , Inibidores da Colinesterase , Cinamatos , Animais , Humanos , Masculino , Camundongos , Acetilcolinesterase/metabolismo , Aminas/química , Aminas/farmacologia , Barreira Hematoencefálica/metabolismo , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/farmacocinética , Inibidores da Colinesterase/metabolismo , Cinamatos/química , Cinamatos/farmacologia , Cinamatos/farmacocinética , Descoberta de Drogas , Estrutura Molecular , Relação Estrutura-Atividade , Pirrolidinas/química , Pirrolidinas/farmacologia , Morfolinas/química , Morfolinas/farmacologia , Piperidinas/química , Piperidinas/farmacologiaRESUMO
BACKGROUND: Saffron has gained people's attention and love for its unique flavor and valuable edible value, but the problem of saffron adulteration in the market is serious. It is urgent for us to find a simple and rapid identification and quantitative estimation of adulteration in saffron. Therefore, excitation-emission matrix (EEM) fluorescence combined with multi-way chemometrics was proposed for the detection and quantification of adulteration in saffron. RESULTS: The fluorescence composition analysis of saffron and saffron adulterants (safflower, marigold and madder) were accomplished by alternating trilinear decomposition (ATLD) algorithm. ATLD and two-dimensional principal component analysis combined with k-nearest neighbor (ATLD-kNN and 2DPCA-kNN) and ATLD combined with data-driven soft independent modeling of class analogies (ATLD-DD-SIMCA) were applied to rapid detection of adulteration in saffron. 2DPCA-kNN and ATLD-DD-SIMCA methods were adopted for the classification of chemical EEM data, first with 100% correct classification rate. The content of adulteration of adulterated saffron was predicted by the N-way partial least squares regression (N-PLS) algorithm. In addition, new samples were correctly classified and the adulteration level in adulterated saffron was estimated semi-quantitatively, which verifies the reliability of these models. CONCLUSION: ATLD-DD-SIMCA and 2DPCA-kNN are recommended methods for the classification of pure saffron and adulterated saffron. The N-PLS algorithm shows potential in prediction of adulteration levels. These methods are expected to solve more complex problems in food authenticity. © 2023 Society of Chemical Industry.
Assuntos
Crocus , Humanos , Crocus/química , Reprodutibilidade dos Testes , Quimiometria , Contaminação de Alimentos/análise , Alimentos , Análise dos Mínimos QuadradosRESUMO
A self-assembled fluorescent nanosensor for the determination of L-cysteine (Cys) was constructed based on the mechanism of fluorescence resonance energy transfer (FRET). In this system, CdTe/ZnS QDs serve as the energy donor while AuNPs serve as the receptor, resulting in the occurrence of FRET with dramatic fluorescence quenching of the QDs (turn off). Once Cys is added, AuNPs can adsorb Cys, leading to the release of the QDs. The process would inhibit the FRET, which contributed to the recovery of fluorescence (turn on) and an off-on fluorescence aptasensor for Cys detection was constructed accordingly. The linear response range of the fluorescence sensor is from 0.8 to 50 µM, and the detection limit is 0.24 µM. The sensor demonstrates great sensitivity and selectivity to Cys. More importantly, the QD-based sensing platform was successfully used for the detection of Cys in milk samples with high precision and accuracy, indicating the potential of the probe in practical applications.
Assuntos
Compostos de Cádmio , Nanopartículas Metálicas , Pontos Quânticos , Cisteína , Transferência Ressonante de Energia de Fluorescência , Ouro , Telúrio , CorantesRESUMO
A glutathione (GSH) optical sensor with high sensitivity and exceptional selectivity was established for the first time. Zeolitic imidazolate framework-8 (ZIF-8) as a model was used for the first time to entrap Mn2+:ZnS quantum dots (QDs) and a rhodamine B derivative (RBD) by self-assembly. Benefiting from the confinement effect of ZIF-8, the loaded QDs and RBD can be brought into close proximity for energy transfer to occur. In the presence of GSH, the fluorescence resonance energy transfer (FRET) process from the QDs to RBD can be initiated, rendering the fluorescent nanoprobe to exhibit a response to GSH. The fluorescence intensity of Mn2+:ZnS@ZIF-8@RBD decreased with an increase in the GSH concentration in the linear range of 5-120 µM and a detection limit of 1.5 µM. This finding leads to a method for the fluorescence detection of GSH with excellent selectivity over other reactive thiols. Moreover, because of its good accuracy and excellent recovery, the nanoplatform can be applied for GSH sensing in real human serum and urine samples. Hence, the developing probe may be extended to other optical sensing domains or drug carriers and has tremendous potential in the field of biomedicine.
Assuntos
Pontos Quânticos , Zeolitas , Humanos , Transferência Ressonante de Energia de Fluorescência , GlutationaRESUMO
OBJECTIVE: The objective of this preclinical study was to examine the responses of the brain to noxious stimulation in the presence and absence of different modes of spinal cord stimulation (SCS) using blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD-fMRI). MATERIALS AND METHODS: Sprague-Dawley rats were randomized to groups based on the mode of SCS delivered which included tonic stimulation (n = 27), burst stimulation (n = 30), and burst-cycle stimulation (n = 29). The control (sham) group (n = 28) received no SCS. The SCS electrode was inserted between T10 and T12 spinal levels prior to fMRI session. The experimental protocol for fMRI acquisition consisted of an initial noxious stimulation phase, a treatment phase wherein the SCS was turned on concurrently with noxious stimulation, and a residual effect phase wherein the noxious stimulation alone was turned on. The responses were statistically analyzed through paired t-test and the results were presented as z-scores for the quantitative analysis of the fMRI data. RESULTS: The treatment with different SCS modes attenuated the BOLD brain responses to noxious hindlimb stimulation. The tonic, burst, and burst-cycle SCS treatment attenuated BOLD responses in the caudate putamen (CPu), insula (In), and secondary somatosensory cortex (S2). There was little to no corresponding change in sham control in these three regions. The burst and burst-cycle SCS demonstrated greater attenuation of BOLD signals in CPu, In, and S2 compared to tonic stimulation. CONCLUSION: The high-resolution fMRI study using a rat model demonstrated the potential of different SCS modes to act on several pain-matrix-related regions of the brain in response to noxious stimulation. The burst and burst-cycle SCS exhibited greater brain activity reduction in response to noxious hindlimb stimulation in the caudate putamen, insula, and secondary somatosensory cortex compared to tonic stimulation.
Assuntos
Neuralgia , Estimulação da Medula Espinal , Animais , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Ratos , Ratos Sprague-Dawley , Medula Espinal/diagnóstico por imagemRESUMO
Recently, the development of a novel fluorescent (FL) nanoprobe for ratiometric detection of antibiotics in real-world samples has received more and more attention. In this article, the distinctive optical properties of deep-ultraviolet emission, a narrowed full width at half maximum (â¼20 nm) and excitation-independent emission of a carbonized nanoprobe (CNP) were easily prepared by an environmentally friendly approach of solvothermal treatment using melamine as the precursor and H2O as the solvent. The obtained CNP can be further utilized as an efficient ratiometric FL nanoprobe for enrofloxacin (EFC) and feroxacin (FXC) detection based on the fact that the FL quenching of the CNP was accompanied by an FL increase with EFC/FXC based on the inner filter effect (IFE). Under the optimal conditions, excellent linear relationships existed between the relative FL intensity (FL290 nm/FL412 nm, CNP for FL290 nm and antibiotics for FL412 nm) and the concentrations of FXC and EFC in the range of 0.05-500.0 µM and 0.05-200.0 µM, with limits of detection of 21.74 and 22.43 nM (3σ/k), respectively. With the proposed ratiometric FL sensor, FXC and EFC in milk and serum samples can be rapidly and selectively analyzed without tedious pretreatment processes for real-world samples.
Assuntos
Corantes Fluorescentes , EnrofloxacinaRESUMO
PURPOSE: To assess the accuracy of intraocular lens power calculation formulas Barrett Universal II (BUII), Hill-Radial Basis Function (RBF) 3.0, Kane, Ladas Super Formula (LSF), Haigis, Hoffer Q, and SRK/T in primary angle-closure disease (PACD). METHODS: A total of 129 PACD eyes were enrolled. Prediction refraction was calculated for each formula and compared with actual refraction. Accuracy was determined by formula performance index (FPI), median absolute error (MedAE) and percentage of eyes with a prediction error (PE) within ± 0.50D. Subgroup analysis was performed according to axial length (AL). RESULTS: Overall, FPI was ranked as follows: Kane (0.067), RBF 3.0 (0.064), Haigis (0.062), SRK/T (0.060), BUII (0.058), Hoffer Q (0.055), and LSF (0.049). Kane got the highest (71.3%) percentage of eyes with PE within ± 0.50 D. In medium AL eyes (22 mm < AL ≤ 25 mm), FPI ranked the same as in total group. MedAEs were equal across all formulas (P = 0.121). In short eyes (AL ≤ 22 mm), FPI was Kane (0.055), RBF 3.0 (0.050), SRK/T (0.050), Haigis (0.049), BUII (0.047), Hoffer Q (0.045), and LSF (0.033). MedAEs were significantly different across all formulas (P = 0.033). Haigis showed the lowest MedAE (0.35 D), Haigis and Kane got the highest percentage (63.6%) of eyes with PE within ± 0.50 D. CONCLUSION: Kane outperformed in total PACD eyes; RBF 3.0, Haigis, and SRK/T achieved satisfying performance. When dealing with PACD eyes shorter than 22 mm, Kane achieved the best accuracy. RBF 3.0, SRK/T, Haigis, and BUII achieved comparable outcomes. No formula showed superiority over others for medium AL PACD eyes.
Assuntos
Lentes Intraoculares , Facoemulsificação , Comprimento Axial do Olho , Biometria , Humanos , Implante de Lente Intraocular , Óptica e Fotônica , Refração Ocular , Estudos RetrospectivosRESUMO
Traveling phase waves are commonly observed in recordings of the cerebral cortex and are believed to organize behavior across different areas of the brain. We use this as motivation to analyze a one-dimensional network of phase oscillators that are nonlocally coupled via the phase response curve (PRC) and the Dirac delta function. Existence of waves is proven and the dispersion relation is computed. Using the theory of distributions enables us to write and solve an associated stability problem. First and second order perturbation theory is applied to get analytic insight and we show that long waves are stable while short waves are unstable. We apply the results to PRCs that come from mitral neurons. We extend the results to smooth pulse-like coupling by reducing the nonlocal equation to a local one and solving the associated boundary value problem.
Assuntos
Encéfalo , Neurônios , Encéfalo/fisiologia , Rede Nervosa , Neurônios/fisiologiaRESUMO
An asymmetric salamo-based probe molecule (H2 L) was synthesized and characterized structurally. When DMF/H2 O (9:1) was used as the solvent, it was shown probe H2 L has high sensitivity to Cu2+ . Using high-resolution mass spectrometry and theoretical calculation, it was found that probe H2 L could form a more stable complex (1:1) with Cu2+ , the minimum limit of detection (LOD) of H2 L for Cu2+ was calculated as 9.95 × 10-8 M. In addition, probe H2 L could also be used to identify B4 O7 2- under the same detection conditions and the minimum LOD of H2 L for B4 O7 2- was calculated as 4.98 × 10-7 M. At the same time, density functional theory theoretical calculation further proved the flexibility of probe H2 L. Through the action of EDTA, probe H2 L had a cyclic ability to recognize Cu2+ , and showed a better response in the physiological pH range; probe H2 L had the characteristics of fast recognition speed and high efficiency. In addition, with probe H2 L test paper for Cu2+ and B4 O7 2- , the effect was more obvious. Meanwhile, probe H2 L can be used to quantitatively detect Cu2+ in water samples.
Assuntos
Cobre , Corantes Fluorescentes , Limite de Detecção , Solventes , ÁguaRESUMO
PURPOSE: To investigate the morphological features and surgical outcomes of retinitis pigmentosa (RP)-associated anterior subcapsular cataract (ASC). METHODS: Consecutive RP-associated ASC cases were reviewed, and one hundred patients (171 eyes) were included. Anterior segment photographed images by slit-lamp microscope were reviewed. Best-corrected visual acuity (BCVA) was recorded. The cases were classified according to preoperative best BCVA, the area (central, midperipheral and peripheral) and the density (Grade 1, vacuolar/bubble-like; Grade 2, plaque-like/translucent; and Grade 3, fibrotic/opaque) of ASC; subgroup analysis of surgical outcomes was then performed. RESULTS: The mean age was 52.1 ± 13.7 years, and the 41-50-year group had the best BCVA. 13.5% of eyes had BCVA better than 20/63, 30.4% were between 20/400 and 20/63, and 56.1% were worse than 20/400. The percentage of ASCs in the central, midperipheral and peripheral areas was 55.0%, 37.4% and 7.6%, respectively. Postoperative BCVA was improved in the central and midperipheral groups (P < 0.001) but was not in the peripheral group (P = 0.07). The percentage of ASCs in density of Grade 1, 2 and 3 was 11.1%, 38.6% and 50.3%, respectively. Grade 2 and 3 achieved improved postoperative BCVA (P < 0.001), but Grade 1 did not (P = 0.693). CONCLUSIONS: Mostly, ASC is located at the center of the pupillary area and affected the residual vision of RP patients. The patients benefited from cataract removal except for those with ASC extended to peripheral area. Surgery was also recommended for RP with ASC developed to be plaque-like and even fibrotic.
Assuntos
Extração de Catarata , Catarata , Retinose Pigmentar , Adulto , Idoso , Catarata/complicações , Catarata/diagnóstico , Humanos , Pessoa de Meia-Idade , Período Pós-Operatório , Retinose Pigmentar/complicações , Retinose Pigmentar/diagnóstico , Estudos Retrospectivos , Acuidade VisualRESUMO
PURPOSE: To evaluate the accuracy of wavefront-derived objective refraction in pseudophakic eyes. METHODS: Retrospective case series. A total of 356 eyes (356 patients) that underwent phacoemulsification and posterior chamber intraocular lens implantation were included. Noncycloplegic subjective manifest refraction (MR) and objective refraction results from the wavefront aberrometer were obtained and compared. Subgroup analysis of objective refraction at 2.6-mm zone was performed based on axial length (AL) and average keratometry. RESULTS: The biases (at the 2.6-mm, 3-mm, and 4-mm zones) were - 0.29 ± 0.37 D, - 0.53 ± 0.41 D, and - 0.51 ± 0.60 D for sphere; - 0.27 ± 0.36 D, - 0.52 ± 0.38 D, and - 0.53 ± 0.51 D for spherical equivalent (SE); 0.03 ± 0.20 D, 0.03 ± 0.22 D, and 0.04 ± 0.27 D for J0; and 0.01 ± 0.16 D, 0.03 ± 0.22 D, and 0.01 ± 0.22 D for J45, respectively. Objective refraction for sphere, SE, and J0 (at 2.6 mm, 3 mm, and 4 mm) was significantly different from MR (P < 0.05), while J45 values were equal. The objective refraction at 2.6 mm was the most accurate in short eyes (≤ 22.5 mm) with a minimum bias for SE (- 0.15 ± 0.28 D) and highest percentage of SE within ± 0.25 to ± 0.75 D of MR. However, there was no difference between the keratometry subgroups. CONCLUSIONS: The wavefront aberrometer achieved the best accuracy at 2.6 mm in pseudophakic eyes with short AL. It still needs modification to be used as a substitute for MR in such patients.
Assuntos
Facoemulsificação , Testes Visuais , Córnea , Humanos , Refração Ocular , Estudos RetrospectivosRESUMO
A smart chemometrics-assisted strategy that combines the full scan mode of liquid chromatography with mass spectrometry with second-order calibration method based on alternating trilinear decomposition algorithm was developed for the rapid determination of 15 glucocorticoids including the epimers betamethasone and dexamethasone illegally added into face masks. Fifteen glucocorticoids were rapidly eluted (11 min) under a simple elution program. By means of the second-order calibration method, 15 target analytes were successfully quantified in the presence of peak overlaps, unknown interferences and baseline drifts. Notably, the epimers, namely, betamethasone and dexamethasone, were simultaneously quantified by the proposed method under a simple elution program. The average spiked recoveries for all target analytes ranged from 87.3 ± 2.2 to 119.4 ± 5.8%. The validation parameters including sensitivity, selectivity, limit of detection, limit of quantitation, and precision were calculated to validate the accuracy of the proposed method, and the quantitative analysis results were further confirmed by liquid chromatography with tandem mass spectrometry. All results proved that the proposed chemometrics-assisted liquid chromatography with mass spectrometry strategy was an accurate and fast method to determine epimers and multiple glucocorticoids in complex face mask samples.
Assuntos
Glucocorticoides/análise , Máscaras , Algoritmos , Calibragem , Cromatografia Líquida , Espectrometria de MassasRESUMO
Viral myocarditis is a common cardiovascular disease, which seriously endangers the health of people and even leads to sudden unexpected death. MicroRNAs play very important roles in various physical and pathological processes including cardiogenesis and heart diseases. In recent years, miR-20b has been implicated in various diseases such as breast cancer, gastric cancer, hepatocellular carcinoma, cardiovascular diseases. However, the function of miR-20b in the pathological progress of viral myocarditis has not been reported. In this study, we found that miR-20b was up-regulated in mouse heart tissues post Coxsackievirus B3 (CVB3) infection. Bioinformatics analysis identified ZFP-148, a transcription factor that plays essential roles in the regulation of virus replication, is one of the predicted targets of miR-20b. MiR-20b expression was found to be up-regulated and ZFP-148 protein level was markedly repressed during viral myocarditis. Further studies demonstrated that miR-20b directly binds to the 3'-UTR of ZFP-148 and suppresses its translation. Moreover, aberrant expression of miR-20b promoted the expression of anti-apoptosis proteins Bcl-2 and Bcl-xL, suggesting that altered gene expression might promote cardiomyocytes survival in viral myocarditis. Our findings indicated that miR-20b might be a potential therapeutic target for CVB3-induced viral myocarditis and a useful marker for the diagnosis of viral myocarditis.
Assuntos
Infecções por Coxsackievirus/genética , Proteínas de Ligação a DNA/genética , MicroRNAs/genética , Miocardite/genética , Fatores de Transcrição/genética , Regiões 3' não Traduzidas , Animais , Apoptose , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , Regulação para Cima , Replicação ViralRESUMO
The Marangoni flow of room temperature liquid metal has recently attracted significant attention in developing advanced flexible drivers. However, most of its induction methods are limited to an external electric field. This study disclosed a new Marangoni flow phenomenon of liquid gallium induced by the gallium-copper galvanic corrosion couple. To better understand this effect, the flow field distribution of liquid gallium was modeled and quantitatively calculated. Then, the intrinsic mechanism of this flow phenomenon was interpreted, during which natural convection and temperature gradient were both excluded and the galvanic corrosion couple was identified as the main reason. In addition, this conclusion was further confirmed by combining the experimental measurement of liquid gallium surface potential and the thermocapillary effect. Moreover, the temperature condition was found to be an indirect factor to the Marangoni flow. This finding broadens the classical understanding of liquid metal surface flow, which also suggests a new way for the application of soft machines.
RESUMO
Multifunctional, highly flexible 3D polypyrrole (PPy) foam is fabricated via a simple electrodeposition method by using nickel foam as the template. The 3D PPy foam has a unique interior structure and is robust enough to manipulate directly.